Skip to main content

Advertisement

SpringerLink
Log in

Zebrafish: a model for the study of addiction genetics

  • Review Paper
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Drug abuse and dependence are multifaceted disorders with complex genetic underpinnings. Identifying specific genetic correlates is challenging and may be more readily accomplished by defining endophenotypes specific for addictive disorders. Symptoms and syndromes, including acute drug response, consumption, preference, and withdrawal, are potential endophenotypes characterizing addiction that have been investigated using model organisms. We present a review of major genes involved in serotonergic, dopaminergic, GABAergic, and adrenoreceptor signaling that are considered to be directly involved in nicotine, opioid, cannabinoid, and ethanol use and dependence. The zebrafish genome encodes likely homologs of the vast majority of these loci. We also review the known expression patterns of these genes in zebrafish. The information presented in this review provides support for the use of zebrafish as a viable model for studying genetic factors related to drug addiction. Expansion of investigations into drug response using model organisms holds the potential to advance our understanding of drug response and addiction in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Ackerman KM, Nakkula R, Zirger JM, Beattie CE, Boyd RT (2009) Cloning and spatiotemporal expression of zebrafish neuronal nicotinic acetylcholine receptor alpha 6 and alpha 4 subunit RNAs. Dev Dyn 238:980–992. doi:10.1002/dvdy.21912

    PubMed  CAS  Google Scholar 

  • ACS ACS (2010) Cancer Facts and Figures 2010. American Cancer Society, Atlanta

    Google Scholar 

  • Agrawal A, Pergadia ML, Balasubramanian S, Saccone SF, Hinrichs AL, Saccone NL, Breslau N, Johnson EO, Hatsukami D, Martin NG, Montgomery GW, Goate AM, Rice JP, Bierut LJ, Madden PA (2009) Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerstrom Test for Nicotine Dependence. Addiction 104:471–477. doi:10.1111/j.1360-0443.2008.02445.x

    PubMed  Google Scholar 

  • Alderman SL, Bernier NJ (2007) Localization of corticotropin-releasing factor, urotensin I, and CRF-binding protein gene expression in the brain of the zebrafish, Danio rerio. J Comp Neurol 502:783–793. doi:10.1002/cne.21332

    PubMed  CAS  Google Scholar 

  • Alexander SP, Mathie A, Peters JA (2008) Guide to receptors and channels (GRAC), 3rd edn. Br J Pharmacol 153(Suppl 2):S1–209. doi:10.1038/sj.bjp.0707746

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410. doi:10.1016/S0022-2836(05)80360-2

    PubMed  CAS  Google Scholar 

  • Alvarez FA, Rodriguez-Martin I, Gonzalez-Nuñez V, de Velasco EMF, Gonzalez Sarmiento R, Rodríguez RE (2006) New kappa opioid receptor from zebrafish Danio rerio. Neurosci Lett 405:94–99. doi:10.1016/j.neulet.2006.06.028

    PubMed  CAS  Google Scholar 

  • Arias A, Feinn R, Kranzler HR (2006) Association of an Asn40Asp (A118G) polymorphism in the mu-opioid receptor gene with substance dependence: a meta-analysis. Drug Alcohol Depend 83:262–268. doi:10.1016/j.drugalcdep.2005.11.024

    PubMed  CAS  Google Scholar 

  • Baraldi PG, Preti D, Materazzi S, Geppetti P (2010) Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. J Med Chem 53:5085–5107. doi:10.1021/jm100062h

    PubMed  CAS  Google Scholar 

  • Bart G, Heilig M, LaForge KS, Pollak L, Leal SM, Ott J, Kreek MJ (2004) Substantial attributable risk related to a functional mu-opioid receptor gene polymorphism in association with heroin addiction in central Sweden. Mol Psychiatry 9:547–549. doi:10.1038/sj.mp.4001504

    PubMed  CAS  Google Scholar 

  • Bellipanni G, Rink E, Bally-Cuif L (2002) Cloning of two tryptophan hydroxylase genes expressed in the diencephalon of the developing zebrafish brain. Mech Dev 119(Suppl 1):S215–S220

    PubMed  Google Scholar 

  • Blin M, Norton W, Bally-Cuif L, Vernier P (2008) NR4A2 controls the differentiation of selective dopaminergic nuclei in the zebrafish brain. Mol Cell Neurosci 39:592–604. doi:10.1016/j.mcn.2008.08.006

    PubMed  CAS  Google Scholar 

  • Boehmler W, Carr T, Thisse C, Thisse B, Canfield VA, Levenson R (2007) D4 Dopamine receptor genes of zebrafish and effects of the antipsychotic clozapine on larval swimming behaviour. Genes Brain Behav 6:155–166. doi:10.1111/j.1601-183X.2006.00243.x

    PubMed  CAS  Google Scholar 

  • Boehmler W, Obrecht-Pflumio S, Canfield V, Thisse C, Thisse B, Levenson R (2004) Evolution and expression of D2 and D3 dopamine receptor genes in zebrafish. Dev Dyn 230:481–493. doi:10.1002/dvdy.20075

    Google Scholar 

  • Braida D, Limonta V, Pegorini S, Zani A, Guerini-Rocco C, Gori E, Sala M (2007) Hallucinatory and rewarding effect of salvinorin A in zebrafish: kappa-opioid and CB1-cannabinoid receptor involvement. Psychopharmacology 190:441–448. doi:10.1007/s00213-006-0639-1

    PubMed  CAS  Google Scholar 

  • Bretaud S, Li Q, Lockwood BL, Kobayashi K, Lin E, Guo S (2007) A choice behavior for morphine reveals experience-dependent drug preference and underlying neural substrates in developing larval zebrafish. Neuroscience 146:1109–1116. doi:10.1016/j.neuroscience.2006.12.073

    PubMed  CAS  Google Scholar 

  • Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB (1997) Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387:303–308. doi:10.1038/387303a0

    PubMed  CAS  Google Scholar 

  • Cabral GA, Raborn ES, Griffin L, Dennis J, Marciano-Cabral F (2008) CB2 receptors in the brain: role in central immune function. Br J Pharmacol 153:240–251. doi:10.1038/sj.bjp.0707584

    PubMed  CAS  Google Scholar 

  • Cachat J, Canavello P, Elegante M, Bartels B, Hart P, Bergner C, Egan R, Duncan A, Tien D, Chung A, Wong K, Goodspeed J, Tan J, Grimes C, Elkhayat S, Suciu C, Rosenberg M, Chung KM, Kadri F, Roy S, Gaikwad S, Stewart A, Zapolsky I, Gilder T, Mohnot S, Beeson E, Amri H, Zukowska Z, Soignier RD, Kalueff AV (2010) Modeling withdrawal syndrome in zebrafish. Behav Brain Res 208:371–376. doi:10.1016/j.bbr.2009.12.004

    PubMed  CAS  Google Scholar 

  • Campa D, Gioia A, Tomei A, Poli P, Barale R (2008) Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clin Pharmacol Ther 83:559–566. doi:10.1038/sj.clpt.6100385

    PubMed  CAS  Google Scholar 

  • Carbone D (1992) Smoking and cancer. Am J Med 93:13S–17S

    PubMed  CAS  Google Scholar 

  • Caron SJC, Prober D, Choy M, Schier AF (2008) In vivo birthdating by BAPTISM reveals that trigeminal sensory neuron diversity depends on early neurogenesis. Development (Cambridge) 135:3259–3269. doi:10.1242/dev.023200

    CAS  Google Scholar 

  • Caudill-Slosberg MA, Schwartz LM, Woloshin S (2004) Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs. 2000. Pain 109:514–519

    PubMed  Google Scholar 

  • Center for Disease Control, Prevention (2007) Unintentional poisoning deaths–United States, 1999–2004. MMWR Morb Mortal Wkly Rep 56:93–96

    Google Scholar 

  • Chandrasekar G, Lauter G, Hauptmann G (2007) Distribution of corticotropin-releasing hormone in the developing zebrafish brain. J Comp Neurol 505:337–351. doi:10.1002/cne.21496

    PubMed  CAS  Google Scholar 

  • Changeux J-P (2010) Nicotine addiction and nicotinic receptors: lessons from genetically modified mice. Nat Rev Neurosci 11:389–401. doi:10.1038/nrn2849

    PubMed  CAS  Google Scholar 

  • Charlton ME, Sweetnam PM, Fitzgerald LW, Terwilliger RZ, Nestler EJ, Duman RS (1997) Chronic ethanol administration regulates the expression of GABAA receptor alpha 1 and alpha 5 subunits in the ventral tegmental area and hippocampus. J Neurochem 68:121–127

    PubMed  CAS  Google Scholar 

  • Chen Y-C, Peng G-S, Wang M-F, Tsao T-P, Yin S-J (2009a) Polymorphism of ethanol-metabolism genes and alcoholism: correlation of allelic variations with the pharmacokinetic and pharmacodynamic consequences. Chemico Biol Interact 178:2–7. doi:10.1016/j.cbi.2008.10.029

    CAS  Google Scholar 

  • Chen Y-C, Priyadarshini M, Panula P (2009b) Complementary developmental expression of the two tyrosine hydroxylase transcripts in zebrafish. Histochem Cell Biol 132:375–381. doi:10.1007/s00418-009-0619-8

    PubMed  CAS  Google Scholar 

  • Cheng W, Guo L, Zhang Z, Soo HM, Wen C, Wu W, Peng J (2006) HNF factors form a network to regulate liver-enriched genes in zebrafish. Dev Biol 294:482–496. doi:10.1016/j.ydbio.2006.03.018

    PubMed  CAS  Google Scholar 

  • Chou WY, Yang LC, Lu HF, Ko JY, Wang CH, Lin SH, Lee TH, Concejero A, Hsu CJ (2006) Association of mu-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty. Acta Anaesthesiol Scand 50:787–792. doi:10.1111/j.1399-6576.2006.01058.x

    PubMed  CAS  Google Scholar 

  • Civelli O, Bunzow JR, Grandy DK (1993) Molecular diversity of the dopamine receptors. Annu Rev Pharmacol Toxicol 33:281–307. doi:10.1146/annurev.pa.33.040193.001433

    PubMed  CAS  Google Scholar 

  • Clark KJ, Balciunas D, Pogoda H-M, Ding Y, Westcot SE, Bedell VM, Greenwood TM, Urban MD, Skuster KJ, Petzold AM, Ni J, Nielsen AL, Patowary A, Scaria V, Sivasubbu S, Xu X, Hammerschmidt M, Ekker SC (2011a) In vivo protein trapping produces a functional expression codex of the vertebrate proteome. Nat Method 8:506–515. doi:10.1038/nmeth.1606

    CAS  Google Scholar 

  • Clark KJ, Boczek NJ, Ekker SC (2011b) Stressing zebrafish for behavioral genetics. Rev Neurosci 22:49–62. doi:10.1515/RNS.2011.007

    PubMed  Google Scholar 

  • Corbett D, Wise RA (1980) Intracranial self-stimulation in relation to the ascending dopaminergic systems of the midbrain: a moveable electrode mapping study. Brain Res 185:1–15

    PubMed  CAS  Google Scholar 

  • Cox JA, Kucenas S, Voigt MM (2005) Molecular characterization and embryonic expression of the family of N-methyl-d-aspartate receptor subunit genes in the zebrafish. Dev Dyn 234:756–766. doi:10.1002/dvdy.20532

    PubMed  CAS  Google Scholar 

  • Crawford DK, Trudell JR, Bertaccini EJ, Li K, Davies DL, Alkana RL (2007) Evidence that ethanol acts on a target in Loop 2 of the extracellular domain of alpha1 glycine receptors. J Neurochem 102:2097–2109. doi:10.1111/j.1471-4159.2007.04680.x

    PubMed  CAS  Google Scholar 

  • Cunningham D, Hawthorn J, Pople A, Gazet JC, Ford HT, Challoner T, Coombes RC (1987) Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. Lancet 1:1461–1463

    PubMed  CAS  Google Scholar 

  • Darland T, Dowling JE (2001) Behavioral screening for cocaine sensitivity in mutagenized zebrafish. Proc Natl Acad Sci USA 98:11691–11696. doi:10.1073/pnas.191380698

    PubMed  CAS  Google Scholar 

  • De Petrocellis L, Orlando P, Moriello AS, Aviello G, Stott C, Izzo A, Di Marzo V (2011) Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiol (Oxf). doi:10.1111/j.1748-1716.2011.02338.x

  • Devignot V, Prado de Carvalho L et al (2003) A novel glycine receptor alpha Z1 subunit variant in the zebrafish brain. Neuroscience 122(2):449–457

    Google Scholar 

  • De Witte P (2004) Imbalance between neuroexcitatory and neuroinhibitory amino acids causes craving for ethanol. Addict Behav 29:1325–1339. doi:10.1016/j.addbeh.2004.06.020

    PubMed  Google Scholar 

  • Delgado L, Schmachtenberg O (2008) Immunohistochemical localization of GABA, GAD65, and the receptor subunits GABAAalpha1 and GABAB1 in the zebrafish cerebellum. Cerebellum 7:444–450. doi:10.1007/s12311-008-0047-7

    PubMed  CAS  Google Scholar 

  • Dhawan BN, Cesselin F, Raghubir R, Reisine T, Bradley PB, Portoghese PS, Hamon M (1996) International union of pharmacology. XII. Classification of opioid receptors. Pharmacol Rev 48:567–592

    PubMed  CAS  Google Scholar 

  • Dick DM, Edenberg HJ, Xuei X, Goate A, Hesselbrock V, Schuckit M, Crowe R, Foroud T (2005) No association of the GABAA receptor genes on chromosome 5 with alcoholism in the collaborative study on the genetics of alcoholism sample. Am J Med Genet B Neuropsychiatr Genet 132B:24–28

    PubMed  Google Scholar 

  • Dick DM, Edenberg HJ, Xuei X, Goate A, Kuperman S, Schuckit M, Crowe R, Smith TL, Porjesz B, Begleiter H, Foroud T (2004) Association of GABRG3 with alcohol dependence. Alcohol Clin Exp Res 28:4–9

    PubMed  CAS  Google Scholar 

  • Djoussé L, Lee I-M, Buring JE, Gaziano JM (2009) Alcohol consumption and risk of cardiovascular disease and death in women: potential mediating mechanisms. Circulation 120:237–244. doi:10.1161/CIRCULATIONAHA.108.832360

    PubMed  Google Scholar 

  • Doldan MJ, Prego B, Holmqvist BI, de Miguel E (1999) Distribution of GABA-immunolabeling in the early zebrafish (Danio rerio) brain. Eur J Morphol 37:126–129

    PubMed  CAS  Google Scholar 

  • Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE, Amora R, Hocking TD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Amacher SL (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26:702–708. doi:10.1038/nbt1409

    PubMed  CAS  Google Scholar 

  • Drakenberg K, Nikoshkov A, Horvath MC, Fagergren P, Gharibyan A, Saarelainen K, Rahman S, Nylander I, Bakalkin G, Rajs J, Keller E, Hurd YL (2006) Mu opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers. Proc Natl Acad Sci USA 103:7883–7888. doi:10.1073/pnas.0600871103

    PubMed  CAS  Google Scholar 

  • Dresen S, Ferreirós N, Pütz M, Westphal F, Zimmermann R, Auwärter V (2010) Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J Mass Spectrom 45:1186–1194. doi:10.1002/jms.1811

    PubMed  CAS  Google Scholar 

  • Durrant R, Thakker J (2003) Substance use and abuse: cultural and historical perspectives. Sage Publications, Thousand Oaks

    Google Scholar 

  • Dworkin S, Heath JK, deJong-Curtain TA, Hogan BM, Lieschke GJ, Malaterre J, Ramsay RG, Mantamadiotis T (2007) CREB activity modulates neural cell proliferation, midbrain-hindbrain organization and patterning in zebrafish. Dev Biol 307:127–141. doi:10.1016/j.ydbio.2007.04.026

    Google Scholar 

  • Edenberg HJ, Dick DM, Xuei X, Tian H, Almasy L, Bauer LO, Crowe RR, Goate A, Hesselbrock V, Jones K, Kwon J, Li TK, Nurnberger JI Jr, O’Connor SJ, Reich T, Rice J, Schuckit MA, Porjesz B, Foroud T, Begleiter H (2004) Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am J Hum Genet 74:705–714 Epub 2004 Mar 12

    PubMed  CAS  Google Scholar 

  • Edenberg HJ, Foroud T (2006) The genetics of alcoholism: identifying specific genes through family studies. Addict Biol 11:386–396

    PubMed  Google Scholar 

  • El-Alfy AT, Ivey K, Robinson K, Ahmed S, Radwan M, Slade D, Khan I, ElSohly M, Ross S (2010) Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacol Biochem Behav 95:434–442. doi:10.1016/j.pbb.2010.03.004

    PubMed  CAS  Google Scholar 

  • Elphick MR, Egertová M (2001) The neurobiology and evolution of cannabinoid signalling. Philos Trans R Soc Lond B Biol Sci 356:381–408. doi:10.1098/rstb.2000.0787

    PubMed  CAS  Google Scholar 

  • Enoch M-A, Gorodetsky E, Hodgkinson C, Roy A, Goldman D (2010) Functional genetic variants that increase synaptic serotonin and 5-HT3 receptor sensitivity predict alcohol and drug dependence. Mol Psychiatry. doi:10.1038/mp.2010.94

  • Enoch M-A, Schuckit MA, Johnson BA, Goldman D (2003) Genetics of alcoholism using intermediate phenotypes. Alcohol Clin Exp Res 27:169–176

    PubMed  Google Scholar 

  • Farris SP, Miles MF (2011) Ethanol modulation of gene networks: implications for alcoholism. Neurobiol Dis. doi:10.1016/j.nbd.2011.04.013

  • Fay JC, Benavides JA (2005) Evidence for domesticated and wild populations of Saccharomyces cerevisiae. PLoS genetics 1:66–71. doi:10.1371/journal.pgen.0010005

    PubMed  CAS  Google Scholar 

  • Filippi A, Dürr K, Ryu S, Willaredt M, Holzschuh J, Driever W (2007) Expression and function of nr4a2, lmx1b, and pitx3 in zebrafish dopaminergic and noradrenergic neuronal development. BMC Dev Biol 7:135. doi:10.1186/1471-213X-7-135

    PubMed  Google Scholar 

  • Fillingim RB, Kaplan L, Staud R, Ness TJ, Glover TL, Campbell CM, Mogil JS, Wallace MR (2005) The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans. J Pain 6:159–167. doi:10.1016/j.jpain.2004.11.008

    PubMed  CAS  Google Scholar 

  • Foley JE, Yeh J-RJ, Maeder ML, Reyon D, Sander JD, Peterson RT, Joung JK (2009) Rapid mutation of endogenous zebrafish genes using zinc finger nucleases made by Oligomerized Pool ENgineering (OPEN). PloS one 4:e4348. doi:10.1371/journal.pone.0004348

    PubMed  Google Scholar 

  • Franke P, Nothen MM, Wang T, Neidt H, Knapp M, Lichtermann D, Weiffenbach O, Mayer P, Hollt V, Propping P, Maier W (1999) Human delta-opioid receptor gene and susceptibility to heroin and alcohol dependence. Am J Med Genet 88:462–464. doi:10.1002/(SICI)1096-8628(19991015)88:5<462::AID-AJMG4>3.0.CO;2-S

    PubMed  CAS  Google Scholar 

  • Gerra G, Leonardi C, Cortese E, D’Amore A, Lucchini A, Strepparola G, Serio G, Farina G, Magnelli F, Zaimovic A, Mancini A, Turci M, Manfredini M, Donnini C (2007) Human kappa opioid receptor gene (OPRK1) polymorphism is associated with opiate addiction. Am J Med Genet B Neuropsychiatr Genet 144B:771–775. doi:10.1002/ajmg.b.30510

    PubMed  CAS  Google Scholar 

  • Goldman D, Oroszi G, Ducci F (2005) The genetics of addictions: uncovering the genes. Nat Rev Genet 6:521–532. doi:10.1038/nrg1635

    PubMed  CAS  Google Scholar 

  • Gonzalez G, Oliveto A, Kosten TR (2002) Treatment of heroin (diamorphine) addiction: current approaches and future prospects. Drugs 62:1331–1343

    PubMed  CAS  Google Scholar 

  • Gonzalez-Nuñez V, Barrallo A, Traynor JR, Rodríguez RE (2006) Characterization of opioid-binding sites in zebrafish brain. J Pharmacol Exp Ther 316:900–904. doi:10.1124/jpet.105.093492

    PubMed  Google Scholar 

  • Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645

    PubMed  Google Scholar 

  • Gotti C, Moretti M, Gaimarri A, Zanardi A, Clementi F, Zoli M (2007) Heterogeneity and complexity of native brain nicotinic receptors. Biochem Pharmacol 74:1102–1111. doi:10.1016/j.bcp.2007.05.023

    PubMed  CAS  Google Scholar 

  • Gotti C, Zoli M, Clementi F (2006) Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol Sci 27:482–491. doi:10.1016/j.tips.2006.07.004

    PubMed  CAS  Google Scholar 

  • Gould TD, Gottesman II (2006) Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav 5:113–119. doi:10.1111/j.1601-183X.2005.00186.x

    PubMed  CAS  Google Scholar 

  • Gruber AJ, Pope HG et al (2003) Attributes of long-term heavy cannabis users: a case-control study. Psychol Med 33(8):1415–1422

    Google Scholar 

  • Guo S, Brush J, Teraoka H, Goddard A, Wilson SW, Mullins MC, Rosenthal A (1999) Development of noradrenergic neurons in the zebrafish hindbrain requires BMP, FGF8, and the homeodomain protein soulless/Phox2a. Neuron 24:555–566

    PubMed  CAS  Google Scholar 

  • Hall AJ, Logan JE, Toblin RL, Kaplan JA, Kraner JC, Bixler D, Crosby AE, Paulozzi LJ (2008) Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA 300:2613–2620

    PubMed  CAS  Google Scholar 

  • Hanchar HJ, Chutsrinopkun P, Meera P, Supavilai P, Sieghart W, Wallner M, Olsen RW (2006) Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15–4513 to alpha4/6beta3delta GABAA receptors. Proc Natl Acad Sci USA 103:8546–8551. doi:10.1073/pnas.0509903103

    PubMed  CAS  Google Scholar 

  • Hannon J, Hoyer D (2008) Molecular biology of 5-HT receptors. Behav Brain Res 195:198–213. doi:10.1016/j.bbr.2008.03.020

    PubMed  CAS  Google Scholar 

  • Harris RA, Trudell JR, Mihic SJ (2008) Ethanol’s molecular targets. Sci Signal 1:re7. doi:10.1126/scisignal.128re7

  • Harwood HJ, Fountain D, Livermore G (1998) Economic costs of alcohol abuse and alcoholism. Recent Dev Alcohol 14:307–330

    Google Scholar 

  • Hayes DJ, Greenshaw AJ (2011) 5-HT receptors and reward-related behaviour: a review. Neurosci Biobehav Rev 35:1419–1449. doi:10.1016/j.neubiorev.2011.03.005

    PubMed  CAS  Google Scholar 

  • Heinrich G, Pagtakhan CJ (2004) Both 5′ and 3′ flanks regulate Zebrafish brain-derived neurotrophic factor gene expression. BMC Neurosci 5:19. doi:10.1186/1471-2202-5-19

    PubMed  Google Scholar 

  • Hirata H, Saint-Amant L et al (2005) Zebrafish bandoneon mutants display behavioral defects due to a mutation in the glycine receptor beta-subunit. Proc Nat Acad Sci USA 102(23):8345–8350

    Google Scholar 

  • Holzschuh J, Ryu S, Aberger F, Driever W (2001) Dopamine transporter expression distinguishes dopaminergic neurons from other catecholaminergic neurons in the developing zebrafish embryo. Mech Dev 101:237–243

    PubMed  CAS  Google Scholar 

  • Howard LA, Ahluwalia JS, Lin S-K, Sellers EM, Tyndale RF (2003) CYP2E1*1D regulatory polymorphism: association with alcohol and nicotine dependence. Pharmacogenetics 13:321–328. doi:10.1097/01.fpc.0000054090.48725.a2

    PubMed  CAS  Google Scholar 

  • Hoyer D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71:533–554

    PubMed  CAS  Google Scholar 

  • Huang P, Xiao A, Zhou M, Zhu Z, Lin S, Zhang B (2011) Heritable gene targeting in zebrafish using customized TALENs. Nat Biotechnol 29:699–700. doi:10.1038/nbt.1939

    PubMed  Google Scholar 

  • Hwang J, Kim H-S, Seok J-W, Kim J-D, Koun S, Park S-Y, Lee J, Kim HS, Kim H-S, Kim KS, Chang K-T, Ryoo ZY, Wang SM, Huh T-l, Lee S (2009) Transcriptome analysis of the zebrafish mind bomb mutant. Mol Genet Genom 281:77–85. doi:10.1007/s00438-008-0395-5

    CAS  Google Scholar 

  • Imboden M, Devignot V et al (2001) Regional distribution of glycine receptor messenger RNA in the central nervous system of zebrafish. Neuroscience 103(3):811–830

    Google Scholar 

  • Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72:165–229

    PubMed  CAS  Google Scholar 

  • Jaffe JH, Kanzler M (1979) Smoking as an addictive disorder. In: Krasnegor NA (ed) Cigarette smoking as a dependence process. NIDA research monograph series, vol 23. U.S. Government Printing Office, ADM:79–800, Washington, DC, pp 4–23

  • Jao L-E, Maddison L, Chen W, Burgess SM (2008) Using retroviruses as a mutagenesis tool to explore the zebrafish genome. Briefings Funct Genom Proteom 7:427–443. doi:10.1093/bfgp/eln038

    CAS  Google Scholar 

  • Jarjour S, Bai L, Gianoulakis C (2009) Effect of acute ethanol administration on the release of opioid peptides from the midbrain including the ventral tegmental area. Alcohol Clin Exp Res 33:1033–1043. doi:10.1111/j.1530-0277.2009.00924.x

    PubMed  CAS  Google Scholar 

  • Jensen AA, Frølund B, Liljefors T, Krogsgaard-Larsen P (2005) Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J Med Chem 48:4705–4745. doi:10.1021/jm040219e

    PubMed  CAS  Google Scholar 

  • Jiménez-Ruiz C, Berlin I, Hering T (2009) Varenicline: a novel pharmacotherapy for smoking cessation. Drugs 69:1319–1338. doi:10.2165/00003495-200969100-00003

    PubMed  Google Scholar 

  • Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380. doi:10.1152/physrev.00019.2008

    PubMed  CAS  Google Scholar 

  • Karlin A (2002) Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci 3:102–114. doi:10.1038/nrn731

    PubMed  CAS  Google Scholar 

  • Kaslin J, Nystedt JM, Ostergård M, Peitsaro N, Panula P (2004) The orexin/hypocretin system in zebrafish is connected to the aminergic and cholinergic systems. J Neurosci 24:2678–2689. doi:10.1523/JNEUROSCI.4908-03.2004

    PubMed  CAS  Google Scholar 

  • Kaslin J, Panula P (2001) Comparative anatomy of the histaminergic and other aminergic systems in zebrafish (Danio rerio). J Comp Neurol 440:342–377

    PubMed  CAS  Google Scholar 

  • Kawakami K, Abe G, Asada T, Asakawa K, Fukuda R, Ito A, Lal P, Mouri N, Muto A, Suster ML, Takakubo H, Urasaki A, Wada H, Yoshida M (2010) zTrap: zebrafish gene trap and enhancer trap database. BMC Dev Biol 10:105. doi:10.1186/1471-213X-10-105

    PubMed  Google Scholar 

  • Kily LJM, Cowe YCM, Hussain O, Patel S, McElwaine S, Cotter FE, Brennan CH (2008) Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways. J Exp Biol 211:1623–1634. doi:10.1242/jeb.014399

    PubMed  CAS  Google Scholar 

  • Kim YJ, Nam RH, Yoo YM, Lee CJ (2004) Identification and functional evidence of GABAergic neurons in parts of the brain of adult zebrafish (Danio rerio). Neurosci Lett 355:29–32

    PubMed  CAS  Google Scholar 

  • Klee EW, Ebbert JO, Schneider H, Hurt RD, Ekker SC (2011) Zebrafish for the study of the biological effects of nicotine. Nicotine Tob Res. doi:10.1093/ntr/ntr010

  • Komoike Y, Shimojima K, Liang JS, Fujii H, Maegaki Y, Osawa M, Fujii S, Higashinakagawa T, Yamamoto T (2010) A functional analysis of GABARAP on 17p13.1 by knockdown zebrafish. J Hum Genet 55:155–162. doi:10.1038/jhg.2010.1

    PubMed  CAS  Google Scholar 

  • Krystal JH, Petrakis IL, Mason G, Trevisan L, D&apos;Souza DC (2003) N-methyl-d-aspartate glutamate receptors and alcoholism: reward, dependence, treatment, and vulnerability. Pharmacol Ther 99:79–94

    Google Scholar 

  • Krystal JH, Staley J, Mason G, Petrakis IL, Kaufman J, Harris RA, Gelernter J, Lappalainen J (2006) Gamma-aminobutyric acid type A receptors and alcoholism: intoxication, dependence, vulnerability, and treatment. Arch Gen Psychiatry 63:957–968. doi:10.1001/archpsyc.63.9.957

    PubMed  CAS  Google Scholar 

  • Kurrasch DM, Nevin LM, Wong JS, Baier H, Ingraham HA (2009) Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish. Neural Dev 4:22. doi:10.1186/1749-8104-4-22

    PubMed  Google Scholar 

  • Lam CS, Rastegar S, Strähle U (2006) Distribution of cannabinoid receptor 1 in the CNS of zebrafish. Neuroscience 138:83–95. doi:10.1016/j.neuroscience.2005.10.069

    PubMed  CAS  Google Scholar 

  • Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23:2947–2948. doi:10.1093/bioinformatics/btm404

    PubMed  CAS  Google Scholar 

  • Lassen N, Estey T, Tanguay RL, Pappa A, Reimers MJ, Vasiliou V (2005) Molecular cloning, baculovirus expression, and tissue distribution of the zebrafish aldehyde dehydrogenase 2. Drug Metabol Dispos Biol Fate Chem 33:649–656. doi:10.1124/dmd.104.002964

    CAS  Google Scholar 

  • Lau B, Bretaud S, Huang Y, Lin E, Guo S (2006) Dissociation of food and opiate preference by a genetic mutation in zebrafish. Genes Brain Behav 5:497–505. doi:10.1111/j.1601-183X.2005.00185.x

    PubMed  CAS  Google Scholar 

  • Leboyer M, Bellivier F, Nosten-Bertrand M, Jouvent R, Pauls D, Mallet J (1998) Psychiatric genetics: search for phenotypes. Trends Neurosci 21:102–105

    PubMed  CAS  Google Scholar 

  • Leuchter AF, Cook IA, Hunter AM, Korb AS (2009) A new paradigm for the prediction of antidepressant treatment response. Dialogues Clinical Neurosci 11:435–446

    Google Scholar 

  • Lewohl JM, Wang L, Miles MF, Zhang L, Dodd PR, Harris RA (2000) Gene expression in human alcoholism: microarray analysis of frontal cortex. Alcohol Clin Exp Res 24:1873–1882

    PubMed  CAS  Google Scholar 

  • Li MD (2008) Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses. Hum Genet 123:119–131. doi:10.1007/s00439-008-0473-0

    PubMed  CAS  Google Scholar 

  • Li MD, Mangold JE, Seneviratne C, Chen GB, Ma JZ, Lou XY, Payne TJ (2009) Association and interaction analyses of GABBR1 and GABBR2 with nicotine dependence in European- and African–American populations. PLoS One 4:e7055

    PubMed  Google Scholar 

  • Li P, Shah S, Huang L, Carr AL, Gao Y, Thisse C, Thisse B, Li L (2007) Cloning and spatial and temporal expression of the zebrafish dopamine D1 receptor. Dev Dyn 236:1339–1346. doi:10.1002/dvdy.21130

    PubMed  CAS  Google Scholar 

  • Lillesaar C, Stigloher C, Tannhäuser B, Wullimann MF, Bally-Cuif L (2009) Axonal projections originating from raphe serotonergic neurons in the developing and adult zebrafish, Danio rerio, using transgenics to visualize raphe-specific pet1 expression. J Comp Neurol 512:158–182. doi:10.1002/cne.21887

    PubMed  CAS  Google Scholar 

  • Lillesaar C, Tannhäuser B, Stigloher C, Kremmer E, Bally-Cuif L (2007) The serotonergic phenotype is acquired by converging genetic mechanisms within the zebrafish central nervous system. Dev Dyn 236:1072–1084. doi:10.1002/dvdy.21095

    PubMed  CAS  Google Scholar 

  • Linden AM, Schmitt U, Leppa E, Wulff P, Wisden W, Luddens H, Korpi ER (2011) Ro 15–4513 antagonizes alcohol-induced sedation in mice through alphabetagamma2-type GABA(A) receptors. Frontiers Neurosci 5:3. doi:10.3389/fnins.2011.00003

    CAS  Google Scholar 

  • Loh EW, Tang NL, Lee DT, Liu SI, Stadlin A (2007) Association analysis of GABA receptor subunit genes on 5q33 with heroin dependence in a Chinese male population. Am J Med Genet B Neuropsychiatr Genet 144B:439–443

    PubMed  CAS  Google Scholar 

  • Lohr H, Ryu S, Driever W (2009) Zebrafish diencephalic A11-related dopaminergic neurons share a conserved transcriptional network with neuroendocrine cell lineages. Development 136:1007–1017. doi:10.1242/dev.033878

    PubMed  Google Scholar 

  • Lotsch J, von Hentig N, Freynhagen R, Griessinger N, Zimmermann M, Doehring A, Rohrbacher M, Sittl R, Geisslinger G (2009) Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers. Pharmacogenet Genom 19:429–436

    Google Scholar 

  • Lou XY, Ma JZ, Sun D, Payne TJ, Li MD (2007) Fine mapping of a linkage region on chromosome 17p13 reveals that GABARAP and DLG4 are associated with vulnerability to nicotine dependence in European-Americans. Hum Mol Genet 16:142–153. doi:10.1093/hmg/ddl450

    PubMed  CAS  Google Scholar 

  • Luo X, Kranzler HR, Zuo L, Lappalainen J, Yang B-z, Gelernter J (2006) ADH4 gene variation is associated with alcohol dependence and drug dependence in European Americans: results from HWD tests and case-control association studies. Neuropsychopharmacology 31:1085–1095. doi:10.1038/sj.npp.1300925

    PubMed  CAS  Google Scholar 

  • Luscher B, Fuchs T, Kilpatrick CL (2011) GABAA receptor trafficking-mediated plasticity of inhibitory synapses. Neuron 70:385–409. doi:10.1016/j.neuron.2011.03.024

    PubMed  CAS  Google Scholar 

  • Mahler J, Filippi A, Driever W (2010) DeltaA/DeltaD regulate multiple and temporally distinct phases of notch signaling during dopaminergic neurogenesis in zebrafish. J Neurosci 30:16621–16635. doi:10.1523/JNEUROSCI.4769-10.2010

    PubMed  CAS  Google Scholar 

  • Maldonado R, Berrendero F, Ozaita A, Robledo P (2011) Neurochemical basis of cannabis addiction. Neuroscience. doi:10.1016/j.neuroscience.2011.02.035

  • Manchikanti L (2007) National drug control policy and prescription drug abuse: facts and fallacies. Pain Physician 10:399–424

    PubMed  Google Scholar 

  • Manchikanti L, Singh A (2008) Therapeutic opioids: a ten-year perspective on the complexities and complications of the escalating use, abuse, and nonmedical use of opioids. Pain Physician 11:S63–S88

    PubMed  Google Scholar 

  • Mansour A, Meador-Woodruff JH, Bunzow JR, Civelli O, Akil H, Watson SJ (1990) Localization of dopamine D2 receptor mRNA and D1 and D2 receptor binding in the rat brain and pituitary: an in situ hybridization-receptor autoradiographic analysis. J Neurosci 10:2587–2600

    PubMed  CAS  Google Scholar 

  • Martínez C, Galván S, Garcia-Martin E, Ramos MI, Gutiérrez-Martín Y, Agúndez JAG (2010) Variability in ethanol biodisposition in whites is modulated by polymorphisms in the ADH1B and ADH1C genes. Hepatology (Baltimore) 51:491–500. doi:10.1002/hep.23341

    Google Scholar 

  • Mathur P, Guo S (2010) Use of zebrafish as a model to understand mechanisms of addiction and complex neurobehavioral phenotypes. Neurobiology Disease 40:66–72. doi:10.1016/j.nbd.2010.05.016

    CAS  Google Scholar 

  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564. doi:10.1038/346561a0

    PubMed  CAS  Google Scholar 

  • Mayer P, Rochlitz H, Rauch E, Rommelspacher H, Hasse HE, Schmidt S, Hollt V (1997) Association between a delta opioid receptor gene polymorphism and heroin dependence in man. Neuroreport 8:2547–2550

    PubMed  CAS  Google Scholar 

  • McDearmid JR, Liao M et al (2006) Glycine receptors regulate interneuron differentiation during spinal network development. Proc Nat Acad Sci USA 103(25):9679–9684

    Google Scholar 

  • McGovern PE, Zhang J, Tang J, Zhang Z, Hall GR, Moreau RA, Nuñez A, Butrym ED, Richards MP, Wang C-S, Cheng G, Zhao Z, Wang C (2004) Fermented beverages of pre- and proto-historic China. Proc Natl Acad Sci USA 101:17593–17598. doi:10.1073/pnas.0407921102

    PubMed  CAS  Google Scholar 

  • McHugh D, Hu SS, Rimmerman N, Juknat A, Vogel Z, Walker JM, Bradshaw HB (2010) N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci 11:44. doi:10.1186/1471-2202-11-44

    PubMed  Google Scholar 

  • McLean DL, Fetcho JR (2004a) Ontogeny and innervation patterns of dopaminergic, noradrenergic, and serotonergic neurons in larval zebrafish. J Comp Neurol 480:38–56. doi:10.1002/cne.20280

    PubMed  Google Scholar 

  • McLean DL, Fetcho JR (2004b) Relationship of tyrosine hydroxylase and serotonin immunoreactivity to sensorimotor circuitry in larval zebrafish. J Comp Neurol 480:57–71. doi:10.1002/cne.20281

    PubMed  Google Scholar 

  • Meera P, Olsen RW, Otis TS, Wallner M (2010) Alcohol- and alcohol antagonist-sensitive human GABAA receptors: tracking delta subunit incorporation into functional receptors. Mol Pharmacol 78:918–924. doi:10.1124/mol.109.062687

    PubMed  CAS  Google Scholar 

  • Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 26:695–701. doi:10.1038/nbt1398

    PubMed  CAS  Google Scholar 

  • Mittleman MA, Lewis RA et al (2001) Triggering myocardial infarction by marijuana. Circulation 103(23):2805–2809

    Google Scholar 

  • Mohrlüder J, Schwarten M, Willbold D (2009) Structure and potential function of gamma-aminobutyrate type A receptor-associated protein. FEBS J 276:4989–5005. doi:10.1111/j.1742-4658.2009.07207.x

    PubMed  Google Scholar 

  • Mongeon R, Gleason MR et al (2008) Synaptic homeostasis in a zebrafish glial glycine transporter mutant. J Neurophysiol 100(4):1716–1723

    Google Scholar 

  • Monsma FJ, Mahan LC, McVittie LD, Gerfen CR, Sibley DR (1990) Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. Proc Natl Acad Sci USA 87:6723–6727

    PubMed  CAS  Google Scholar 

  • Moonat S, Starkman BG, Sakharkar A, Pandey SC (2010) Neuroscience of alcoholism: molecular and cellular mechanisms. CMLS 67:73–88. doi:10.1007/s00018-009-0135-y

    PubMed  CAS  Google Scholar 

  • Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65. doi:10.1038/365061a0

    PubMed  CAS  Google Scholar 

  • Murakami M (2011) Lipid mediators in life science. Exp Anim Tokyo 60:7–20

    CAS  Google Scholar 

  • Nguyen-Legros J, Versaux-Botteri C, Vernier P (1999) Dopamine receptor localization in the mammalian retina. Mol Neurobiol 19:181–204. doi:10.1007/BF02821713

    PubMed  CAS  Google Scholar 

  • Nielsen DA, Barral S, Proudnikov D, Kellogg S, Ho A, Ott J, Kreek MJ (2008) TPH2 and TPH1: association of variants and interactions with heroin addiction. Behav Genet 38:133–150. doi:10.1007/s10519-007-9187-7

    PubMed  Google Scholar 

  • Ninkovic J, Bally-Cuif L (2006) The zebrafish as a model system for assessing the reinforcing properties of drugs of abuse. Methods 39:262–274. doi:10.1016/j.ymeth.2005.12.007

    PubMed  CAS  Google Scholar 

  • Nishimura FT, Fukunaga T, Kajiura H, Umeno K, Takakura H, Ono T, Nishijo H (2002) Effects of aldehyde dehydrogenase-2 genotype on cardiovascular and endocrine responses to alcohol in young Japanese subjects. Auton Neurosci Basic Clinical 102:60–70

    CAS  Google Scholar 

  • Norton WHJ, Folchert A, Bally-Cuif L (2008) Comparative analysis of serotonin receptor (HTR1A/HTR1B families) and transporter (slc6a4a/b) gene expression in the zebrafish brain. J Comp Neurol 511:521–542. doi:10.1002/cne.21831

    PubMed  CAS  Google Scholar 

  • Nusslein-Volhard C (2002) Zebrafish—a practical approach, 1st edn. Oxford University Press, Oxford

    Google Scholar 

  • Nutt DJ, King LA, Phillips LD, ISCo Drugs (2010) Drug harms in the UK: a multicriteria decision analysis. Lancet 376:1558–1565. doi:10.1016/S0140-6736(10)61462-6

    PubMed  Google Scholar 

  • O’Dowd BF (1993) Structures of dopamine receptors. J Neurochem 60:804–816

    Google Scholar 

  • Olsen Y, Daumit GL, Ford DE (2006) Opioid prescriptions by US primary care physicians from 1992 to 2001. J Pain 7:225–235

    PubMed  Google Scholar 

  • Onaivi ES (2006) Neuropsychobiological evidence for the functional presence and expression of cannabinoid CB2 receptors in the brain. Neuropsychobiology 54:231–246. doi:10.1159/000100778

    PubMed  CAS  Google Scholar 

  • Overton HA, Babbs AJ, Doel SM, Fyfe MCT, Gardner LS, Griffin G, Jackson HC, Procter MJ, Rasamison CM, Tang-Christensen M, Widdowson PS, Williams GM, Reynet C (2006) Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab 3:167–175. doi:10.1016/j.cmet.2006.02.004

    PubMed  CAS  Google Scholar 

  • Panula P, Chen Y-C, Priyadarshini M, Kudo H, Semenova S, Sundvik M, Sallinen V (2010) The comparative neuroanatomy and neurochemistry of zebrafish CNS systems of relevance to human neuropsychiatric diseases. Neurobiol Dis 40:46–57. doi:10.1016/j.nbd.2010.05.010

    PubMed  CAS  Google Scholar 

  • Parsian A, Zhang ZH (1999) Human chromosomes 11p15 and 4p12 and alcohol dependence: possible association with the GABRB1 gene. Am J Med Genet 88:533–538

    PubMed  CAS  Google Scholar 

  • Paulozzi LJ, Budnitz DS, Xi Y (2006) Increasing deaths from opioid analgesics in the United States. Pharmacoepidemiol Drug Saf 15:618–627

    PubMed  Google Scholar 

  • Paulozzi LJ, Ryan GW (2006) Opioid analgesics and rates of fatal drug poisoning in the United States. Am J Prev Med 31:506–511

    PubMed  Google Scholar 

  • Pertwee RG, Howlett AC, Abood ME, Alexander SPH, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 62:588–631. doi:10.1124/pr.110.003004

    PubMed  CAS  Google Scholar 

  • Petzold AM, Balciunas D, Sivasubbu S, Clark KJ, Bedell VM, Westcot SE, Myers SR, Moulder GL, Thomas MJ, Ekker SC (2009) Nicotine response genetics in the zebrafish. Proc Nat Acad Sci 106:18662–18667. doi:10.1073/pnas.0908247106

    PubMed  CAS  Google Scholar 

  • Pfaar H, von Holst A, Vogt Weisenhorn DM, Brodski C, Guimera J, Wurst W (2002) mPet-1, a mouse ETS-domain transcription factor, is expressed in central serotonergic neurons. Dev Genes Evol 212:43–46. doi:10.1007/s00427-001-0208-x

    PubMed  CAS  Google Scholar 

  • Piccinetti CC, Migliarini B, Olivotto I, Coletti G, Amici A, Carnevali O (2010) Appetite regulation: the central role of melatonin in Danio rerio. Horm Behav 58:780–785. doi:10.1016/j.yhbeh.2010.07.013

    PubMed  CAS  Google Scholar 

  • Pinal-Seoane N, Martin IR, Gonzalez-Nuñez V, de Velasco EMF, Alvarez FA, Sarmiento RG, Rodríguez RE (2006) Characterization of a new duplicate delta-opioid receptor from zebrafish. J Mol Endocrinol 37:391–403. doi:10.1677/jme.1.02136

    PubMed  CAS  Google Scholar 

  • Pinard A, Seddik R, Bettler B (2010) GABAB receptors: physiological functions and mechanisms of diversity. Adv Pharmacol (San Diego) 58:231–255. doi:10.1016/S1054-3589(10)58010-4

    CAS  Google Scholar 

  • Pope HG, Gruber AJ et al (2001) Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry 58(10):909–915

    Google Scholar 

  • Prober DA, Zimmerman S, Myers BR, McDermott BM, Kim S-H, Caron S, Rihel J, Solnica-Krezel L, Julius D, Hudspeth AJ, Schier AF (2008) Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function. J Neurosci 28:10102–10110. doi:10.1523/JNEUROSCI.2740-08.2008

    PubMed  CAS  Google Scholar 

  • Radel M, Vallejo RL, Iwata N, Aragon R, Long JC, Virkkunen M, Goldman D (2005) Haplotype-based localization of an alcohol dependence gene to the 5q34 {gamma}-aminobutyric acid type A gene cluster. Arch Gen Psychiatry 62:47–55

    PubMed  CAS  Google Scholar 

  • Ramchandani VA, Umhau J, Pavon FJ, Ruiz-Velasco V, Margas W, Sun H, Damadzic R, Eskay R, Schoor M, Thorsell A, Schwandt ML, Sommer WH, George DT, Parsons LH, Herscovitch P, Hommer D, Heilig M (2011) A genetic determinant of the striatal dopamine response to alcohol in men. Mol Psychiatry 16:809–817. doi:10.1038/mp.2010.56

    PubMed  CAS  Google Scholar 

  • Rauch G, Lyons D, Middendorf I, Friedlander B, Arana N, Reyes T, Talbot W (2003) Submission and curation of gene expression data. http://www.zfin.org

  • Ray R, Jepson C, Patterson F, Strasser A, Rukstalis M, Perkins K, Lynch KG, O’Malley S, Berrettini WH, Lerman C (2006) Association of OPRM1 A118G variant with the relative reinforcing value of nicotine. Psychopharmacology (Berl) 188:355–363. doi:10.1007/s00213-006-0504-2

    CAS  Google Scholar 

  • Reck BH, Mukhopadhyay N, Tsai HJ, Weeks DE (2005) Analysis of alcohol dependence phenotype in the COGA families using covariates to detect linkage. BMC Genet 6:S143

    PubMed  Google Scholar 

  • Rehm Room, Monteiro Gmel, Graham Rehn (2004) Comparative quantification of health risks: global and regional burden of disease due to selected major risk factors. WHO, Geneva, pp 959–1108

    Google Scholar 

  • Reyes-Gibby CC, Shete S, Rakvag T, Bhat SV, Skorpen F, Bruera E, Kaasa S, Klepstad P (2007) Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain 130:25–30. doi:10.1016/j.pain.2006.10.023

    PubMed  CAS  Google Scholar 

  • Rink E, Guo S (2004) The too few mutant selectively affects subgroups of monoaminergic neurons in the zebrafish forebrain. Neuroscience 127:147–154. doi:10.1016/j.neuroscience.2004.05.004

    PubMed  CAS  Google Scholar 

  • Rink E, Wullimann MF (2001) The teleostean (zebrafish) dopaminergic system ascending to the subpallium (striatum) is located in the basal diencephalon (posterior tuberculum). Brain Res 889:316–330

    PubMed  CAS  Google Scholar 

  • Rink E, Wullimann MF (2002a) Connections of the ventral telencephalon and tyrosine hydroxylase distribution in the zebrafish brain (Danio rerio) lead to identification of an ascending dopaminergic system in a teleost. Brain Res Bull 57:385–387

    PubMed  CAS  Google Scholar 

  • Rink E, Wullimann MF (2002b) Development of the catecholaminergic system in the early zebrafish brain: an immunohistochemical study. Dev Brain Res 137:89–100

    CAS  Google Scholar 

  • Rios Y, Melmed S, Lin S, Liu NA (2011) Zebrafish usp39 mutation leads to rb1 mRNA splicing defect and pituitary lineage expansion. PLoS genetics 7:e1001271. doi:10.1371/journal.pgen.1001271

    PubMed  CAS  Google Scholar 

  • Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, Hood LE, Aderem A (2005) The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci USA 102:9577–9582. doi:10.1073/pnas.0502272102

    PubMed  CAS  Google Scholar 

  • Rodd ZA, Kimpel MW, Edenberg HJ, Bell RL, Strother WN, McClintick JN, Carr LG, Liang T, McBride WJ (2008) Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats. Pharmacol Biochem Behav 89:481–498 Epub 2008 Feb 26

    PubMed  CAS  Google Scholar 

  • Rodriguez-Martin I, Herrero-Turrion MJ, Fdez Marron, de Velasco E, Gonzalez-Sarmiento R, Rodríguez RE (2007) Characterization of two duplicate zebrafish Cb2-like cannabinoid receptors. Gene 389:36–44. doi:10.1016/j.gene.2006.09.016

    PubMed  CAS  Google Scholar 

  • Ross RA (2003) Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 140:790–801. doi:10.1038/sj.bjp.0705467

    PubMed  CAS  Google Scholar 

  • Rucktooa P, Smit AB, Sixma TK (2009) Insight in nAChR subtype selectivity from AChBP crystal structures. Biochem Pharmacol 78:777–787. doi:10.1016/j.bcp.2009.06.098

    PubMed  CAS  Google Scholar 

  • Ruuskanen JO, Peitsaro N, Kaslin JVM, Panula P, Scheinin M (2005) Expression and function of alpha-adrenoceptors in zebrafish: drug effects, mRNA and receptor distributions. J Neurochem 94:1559–1569. doi:10.1111/j.1471-4159.2005.03305.x

    PubMed  CAS  Google Scholar 

  • Ruuskanen JO, Xhaard H, Marjamäki A, Salaneck E, Salminen T, Yan Y-L, Postlethwait JH, Johnson MS, Larhammar D, Scheinin M (2004) Identification of duplicated fourth alpha2-adrenergic receptor subtype by cloning and mapping of five receptor genes in zebrafish. Mol Biol Evol 21:14–28. doi:10.1093/molbev/msg224

    PubMed  CAS  Google Scholar 

  • Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson N-O, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2009) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101. doi:10.1038/sj.bjp.0707460

    Google Scholar 

  • Sallinen V, Sundvik M, Reenilä I, Peitsaro N, Khrustalyov D, Anichtchik O, Toleikyte G, Kaslin J, Panula P (2009) Hyperserotonergic phenotype after monoamine oxidase inhibition in larval zebrafish. J Neurochem 109:403–415. doi:10.1111/j.1471-4159.2009.05986.x

    PubMed  CAS  Google Scholar 

  • Sanchez-Simon FM, Rodríguez RE (2008) Developmental expression and distribution of opioid receptors in zebrafish. Neuroscience 151:129–137. doi:10.1016/j.neuroscience.2007.09.086

    PubMed  CAS  Google Scholar 

  • Sanchez-Simon FM, Zhang XX, Loh HH, Law PY, Rodriguez RE (2010) Morphine regulates dopaminergic neuron differentiation via miR-133b. Mol Pharmacol 78:935–942. doi:10.1124/mol.110.066837

    PubMed  CAS  Google Scholar 

  • Sandell JH, Martin SC, Heinrich G (1994) The development of GABA immunoreactivity in the retina of the zebrafish (Brachydanio rerio). J Comp Neurol 345:596–601. doi:10.1002/cne.903450409

    PubMed  CAS  Google Scholar 

  • Sander T, Ball D, Murray R, Patel J, Samochowiec J, Winterer G, Rommelspacher H, Schmidt LG, Loh EW (1999) Association analysis of sequence variants of GABA(A) alpha6, beta2, and gamma2 gene cluster and alcohol dependence. Alcohol Clin Exp Res 23:427–431

    PubMed  CAS  Google Scholar 

  • Sanders-Bush E, Fentress H, Hazelwood L (2003) Serotonin 5-ht2 receptors: molecular and genomic diversity. Mol Interv 3:319–330. doi:10.1124/mi.3.6.319

    PubMed  CAS  Google Scholar 

  • Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80:1–27

    PubMed  CAS  Google Scholar 

  • Schultz W (2010) Dopamine signals for reward value and risk: basic and recent data. Behav Brain Funct 6:24. doi:10.1186/1744-9081-6-24

    PubMed  Google Scholar 

  • Scott MM, Krueger KC, Deneris ES (2005) A differentially autoregulated Pet-1 enhancer region is a critical target of the transcriptional cascade that governs serotonin neuron development. J Neurosci 25:2628–2636. doi:10.1523/JNEUROSCI.4979-04.2005

    PubMed  CAS  Google Scholar 

  • Shippenberg TS, Chefer VI, Zapata A, Heidbreder CA (2001) Modulation of the behavioral and neurochemical effects of psychostimulants by kappa-opioid receptor systems. Ann N Y Acad Sci 937:50–73

    PubMed  CAS  Google Scholar 

  • Sia AT, Lim Y, Lim EC, Goh RW, Law HY, Landau R, Teo YY, Tan EC (2008) A118G single nucleotide polymorphism of human mu-opioid receptor gene influences pain perception and patient-controlled intravenous morphine consumption after intrathecal morphine for postcesarean analgesia. Anesthesiology 109:520–526. doi:10.1097/ALN.0b013e318182af21

    PubMed  CAS  Google Scholar 

  • Sieh W, Basu S, Fu AQ, Rothstein JH, Scheet PA, Stewart WC, Sung YJ, Thompson EA, Wijsman EM (2005) Comparison of marker types and map assumptions using Markov chain Monte Carlo-based linkage analysis of COGA data. BMC Genet 6:S11

    PubMed  Google Scholar 

  • Smith TH, Sim-Selley LJ, Selley DE (2010) Cannabinoid CB1 receptor-interacting proteins: novel targets for central nervous system drug discovery? Br J Pharmacol 160:454–466. doi:10.1111/j.1476-5381.2010.00777.x

    PubMed  CAS  Google Scholar 

  • Song J, Koller DL, Foroud T, Carr K, Zhao J, Rice J, Nurnberger JI Jr, Begleiter H, Porjesz B, Smith TL, Schuckit MA, Edenberg HJ (2003) Association of GABA(A) receptors and alcohol dependence and the effects of genetic imprinting. Am J Med Genet B Neuropsychiatr Genet 117B:39–45

    PubMed  Google Scholar 

  • Song W, Zou Z, Xu F, Gu X, Xu X, Zhao Q (2006) Molecular cloning and expression of a second zebrafish aldehyde dehydrogenase 2 gene (aldh2b). DNA Seq J DNA Seq mapp 17:262–269

    CAS  Google Scholar 

  • Steinbusch HW (1981) Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 6:557–618

    PubMed  CAS  Google Scholar 

  • Steinbusch HW, Nieuwenhuys R (1981) Localization of serotonin-like immunoreactivity in the central nervous system and pituitary of the rat, with special references to the innervation of the hypothalamus. Adv Exp Med Biol 133:7–35

    PubMed  CAS  Google Scholar 

  • Stewart A, Wong K, Cachat J, Gaikwad S, Kyzar E, Wu N, Hart P, Piet V, Utterback E, Elegante M, Tien D, Kalueff AV (2011) Zebrafish models to study drug abuse-related phenotypes. Rev Neurosci 22:95–105. doi:10.1515/RNS.2011.011

    PubMed  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (2010) Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4586 Findings). Rockville, MD

  • Sullivan C, Charette J, Catchen J, Lage CR, Giasson G, Postlethwait JH, Millard PJ, Kim CH (2009) The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions. J Immunol 183:5896–5908. doi:10.4049/jimmunol.0803285

    PubMed  CAS  Google Scholar 

  • Sun Y, Alexander SPH, Garle MJ, Gibson CL, Hewitt K, Murphy SP, Kendall DA, Bennett AJ (2007) Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism. Br J Pharmacol 152:734–743. doi:10.1038/sj.bjp.0707478

    PubMed  CAS  Google Scholar 

  • Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739. doi:10.1093/molbev/msr121

    PubMed  CAS  Google Scholar 

  • Tan KR, Rudolph U, Luscher C (2011) Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci 34:188–197 Epub 2011 Feb 25

    PubMed  CAS  Google Scholar 

  • Tassin J-P (2008) Uncoupling between noradrenergic and serotonergic neurons as a molecular basis of stable changes in behavior induced by repeated drugs of abuse. Biochem Pharmacol 75:85–97. doi:10.1016/j.bcp.2007.06.038

    PubMed  CAS  Google Scholar 

  • Tay TL, Ronneberger O, Ryu S, Nitschke R, Driever W (2011) Comprehensive catecholaminergic projectome analysis reveals single-neuron integration of zebrafish ascending and descending dopaminergic systems. Nat Commun 2:171. doi:10.1038/ncomms1171

    PubMed  Google Scholar 

  • Thisse B, Pflumino S, Furthauer M, Loppin B, Heyer V, Degrave A, Woehl R, Lux A, Steffan T, Charbonnier XQ, Thisse C (2001) Expression of the zebrafish genome during embryogenesis. http://www.zfin.org

  • Thisse B, Thisse C (2004) Fast release clones: a high throughput expression analysis. http://www.zfin.org

  • Thisse C, Thisse B (2005) High throughput expression analysis of ZF-models consortium clones. http://www.zfin.org

  • Thomas DR (2006) 5-ht5A receptors as a therapeutic target. Pharmacol Ther 111:707–714. doi:10.1016/j.pharmthera.2005.12.006

    PubMed  CAS  Google Scholar 

  • Törk I (1990) Anatomy of the serotonergic system. Ann N Y Acad Sci 600:9–34 discussion 34–5

    PubMed  Google Scholar 

  • Tsai G, Coyle JT (1998) The role of glutamatergic neurotransmission in the pathophysiology of alcoholism. Annu Rev Med 49:173–184. doi:10.1146/annurev.med.49.1.173

    PubMed  CAS  Google Scholar 

  • Tyacke RJ, Lingford-Hughes A, Reed LJ, Nutt DJ (2010) GABAB receptors in addiction and its treatment. Adv Pharmacol 58:373–396

    PubMed  CAS  Google Scholar 

  • Ueda N, Tsuboi K, Uyama T (2010) Enzymological studies on the biosynthesis of N-acylethanolamines. Biochim Biophys Acta 1801:1274–1285. doi:10.1016/j.bbalip.2010.08.010

    PubMed  CAS  Google Scholar 

  • Ueda N, Tsuboi K, Uyama T, Ohnishi T (2011) Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol. Biofactors 37:1–7. doi:10.1002/biof.131

    PubMed  CAS  Google Scholar 

  • Veenstra-VanderWeele J, Anderson GM, Cook EH (2000) Pharmacogenetics and the serotonin system: initial studies and future directions. Eur J Pharmacol 410:165–181

    PubMed  CAS  Google Scholar 

  • Vlachou S, Markou A (2010) GABAB receptors in reward processes. Adv Pharmacol (San Diego) 58:315–371. doi:10.1016/S1054-3589(10)58013-X

    CAS  Google Scholar 

  • Volkmann K, Rieger S, Babaryka A, Koster RW (2008) The zebrafish cerebellar rhombic lip is spatially patterned in producing granule cell populations of different functional compartments. Dev Biol 313:167–180. doi:10.1016/j.ydbio.2007.10.024

    PubMed  CAS  Google Scholar 

  • Volkow ND, Fowler JS, Wang G-J, Swanson JM, Telang F (2007) Dopamine in drug abuse and addiction: results of imaging studies and treatment implications. Arch Neurol 64:1575–1579. doi:10.1001/archneur.64.11.1575

    PubMed  Google Scholar 

  • Wagner FA, Anthony JC (2002) From first drug use to drug dependence; developmental periods of risk for dependence upon marijuana, cocaine, and alcohol. Neuropsychopharmacology 26:479–488. doi:10.1016/S0893-133X(01)00367-0

    PubMed  Google Scholar 

  • Walstab J, Rappold G, Niesler B (2010) 5-HT(3) receptors: role in disease and target of drugs. Pharmacol Ther 128:146–169. doi:10.1016/j.pharmthera.2010.07.001

    PubMed  CAS  Google Scholar 

  • Walter C, Lotsch J (2009) Meta-analysis of the relevance of the OPRM1 118A > G genetic variant for pain treatment. Pain 146:270–275. doi:10.1016/j.pain.2009.07.013

    PubMed  CAS  Google Scholar 

  • Wang Z, Nishimura Y, Shimada Y, Umemoto N, Hirano M, Zang L, Oka T, Sakamoto C, Kuroyanagi J, Tanaka T (2009) Zebrafish beta-adrenergic receptor mRNA expression and control of pigmentation. Gene 446:18–27. doi:10.1016/j.gene.2009.06.005

    PubMed  CAS  Google Scholar 

  • Watson S, Chambers D, Hobbs C, Doherty P, Graham A (2008) The endocannabinoid receptor, CB1, is required for normal axonal growth and fasciculation. Mol Cell Neurosci 38:89–97. doi:10.1016/j.mcn.2008.02.001

    PubMed  CAS  Google Scholar 

  • Welsh L, Tanguay RL, Svoboda KR (2009) Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish. Toxicol Appl Pharmacol 237:29–40. doi:10.1016/j.taap.2008.06.025

    PubMed  CAS  Google Scholar 

  • WHO WHO (2008) WHO Report on the global tobacco epideminc. WHO Press, Geneva

    Google Scholar 

  • Wick MJ, Mihic SJ, Ueno S, Mascia MP, Trudell JR, Brozowski SJ, Ye Q, Harrison NL, Harris RA (1998) Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor? Proc Natl Acad Sci USA 95:6504–6509

    PubMed  CAS  Google Scholar 

  • Woolfit M, Wolfe K (2005) The gene duplication that greased society&apos;s wheels. Nat Genet 37:566–567. doi:10.1038/ng0605-566

    PubMed  CAS  Google Scholar 

  • Wysowski DK (2007) Surveillance of prescription drug-related mortality using death certificate data. Drug Saf 30:533–540

    PubMed  Google Scholar 

  • Xi ZX, Peng XQ, Li X, Song R, Zhang HY, Liu QR, Yang HJ, Bi GH, Li J, Gardner EL (2011) Brain cannabinoid CB receptors modulate cocaine’s actions in mice. Nat Neurosci 14:1160–1166. doi:10.1038/nn.2874

    PubMed  CAS  Google Scholar 

  • Xu K, Liu XH, Nagarajan S, Gu XY, Goldman D (2002) Relationship of the delta-opioid receptor gene to heroin abuse in a large Chinese case/control sample. Am J Med Genet 110:45–50. doi:10.1002/ajmg.10374

    PubMed  Google Scholar 

  • Xuei X, Dick D, Flury-Wetherill L, Tian HJ, Agrawal A, Bierut L, Goate A, Bucholz K, Schuckit M, Nurnberger J Jr, Tischfield J, Kuperman S, Porjesz B, Begleiter H, Foroud T, Edenberg HJ (2006) Association of the kappa-opioid system with alcohol dependence. Mol Psychiatry 11:1016–1024. doi:10.1038/sj.mp.4001882

    PubMed  CAS  Google Scholar 

  • Yoshimura M, Pearson S, Kadota Y, Gonzalez CE (2006) Identification of ethanol responsive domains of adenylyl cyclase. Alcohol Clin Exp Res 30:1824–1832. doi:10.1111/j.1530-0277.2006.00219.x

    PubMed  CAS  Google Scholar 

  • Yoshimura M, Tabakoff B (1995) Selective effects of ethanol on the generation of cAMP by particular members of the adenylyl cyclase family. Alcohol Clin Exp Res 19:1435–1440

    PubMed  CAS  Google Scholar 

  • Yuferov V, Fussell D, LaForge KS, Nielsen DA, Gordon D, Ho A, Leal SM, Ott J, Kreek MJ (2004) Redefinition of the human kappa opioid receptor gene (OPRK1) structure and association of haplotypes with opiate addiction. Pharmacogenetics 14:793–804 pii: 00008571-200412000-00002

    PubMed  CAS  Google Scholar 

  • Zhang H, Kranzler HR, Yang BZ, Luo X, Gelernter J (2008) The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk. Mol Psychiatry 13:531–543. doi:10.1038/sj.mp.4002035

    PubMed  CAS  Google Scholar 

  • Zhang H, Zhong X, Ye Y (2005) Multivariate linkage analysis using the electrophysiological phenotypes in the COGA alcoholism data. BMC Genet 6:S118

    PubMed  Google Scholar 

  • Zirger JM, Beattie CE, McKay DB, Boyd RT (2003) Cloning and expression of zebrafish neuronal nicotinic acetylcholine receptors. Gene Exp Patterns 3:747–754

    CAS  Google Scholar 

Download references

Acknowledgments

Funding supported for VMK: NIAAA1P20AA017830-0; S.C. Johnson Genomics of Addictions Program. Funding supported for EWK: NIH/NCRR CTSA Grant Number KL2 RR024151. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Funding supported for SCE: NIDA DA14546.

Author information

Authors and Affiliations

  1. Mayo Clinic, Mayo Addiction Research Center, 200 First St SW, Rochester, MN, 55905, USA

    Eric W. Klee, Karl J. Clark, Margot A. Cousin, Jon O. Ebbert, W. Michael Hooten, Victor M. Karpyak, David O. Warner & Stephen C. Ekker

  2. Department of Biology, DePauw University, 1 E. Hanna St, Greencastle, IN, 46135, USA

    Henning Schneider

Authors
  1. Eric W. Klee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henning Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karl J. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Margot A. Cousin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jon O. Ebbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W. Michael Hooten
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Victor M. Karpyak
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David O. Warner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stephen C. Ekker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen C. Ekker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klee, E.W., Schneider, H., Clark, K.J. et al. Zebrafish: a model for the study of addiction genetics. Hum Genet 131, 977–1008 (2012). https://doi.org/10.1007/s00439-011-1128-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-011-1128-0

Keywords

Search

Navigation