, Volume 215, Issue 4, pp 631–642 | Cite as

Genotype-dependent effects of adolescent nicotine exposure on dopamine functional dynamics in the nucleus accumbens shell in male and female mice: a potential mechanism underlying the gateway effect of nicotine

  • Price E. Dickson
  • Tiffany D. Rogers
  • Deranda B. Lester
  • Mellessa M. Miller
  • Shannon G. Matta
  • Elissa J. Chesler
  • Dan Goldowitz
  • Charles D. Blaha
  • Guy Mittleman
Original Investigation



The tendency to use cocaine is determined by genetic and environmental effects across the lifespan. One critical environmental effect is early drug exposure, which is both driven by and interacts with genetic background. The mesoaccumbens dopamine system, which is critically involved in the rewarding properties of drugs of abuse, undergoes significant development during adolescence, and thus may be at particular risk to repeated nicotine exposure during this period, thereby establishing vulnerability for subsequent adult psychostimulant use.


We tested the hypotheses that adolescent nicotine exposure results in attenuation of the enhancing effects of cocaine on medial forebrain bundle (MFB) electrical stimulation-evoked dopamine release in the nucleus accumbens shell (AcbSh) in adulthood and that this effect is significantly influenced by genotype.


Mice from the progenitor strains C57BL/6J and DBA/2J and those from the BXD20/TyJ and BXD86/RwwJ recombinant inbred lines were exposed to nicotine via osmotic minipumps from postnatal day (P) 28 to P56. When mice reached P70, dopamine functional dynamics in AcbSh was evaluated by means of in vivo fixed potential amperometry in combination with electrical stimulation of mesoaccumbens dopaminergic axons in the MFB.


Adolescent exposure to nicotine in all strains dose-dependently reduced the ability of a fixed-dose challenge injection of cocaine (10 mg/kg, i.p.) to enhance MFB electrical stimulation-evoked dopamine release in AcbSh in adults. The magnitude of this effect was genotype-dependent.


These results suggest a genotype-dependent mechanism by which nicotine exposure during adolescence causes persistent changes in the sensitivity to “hard” stimulants such as cocaine.


Nicotine Dopamine BXD C57BL/6J DBA/2J Minipump Electrochemistry Amperometry Body weight Cocaine 



This project was made possible by a Dunavant Professorship awarded to GM. For their assistance with data collection, the authors thank Erin Clardy and Tom Schneider.

Conflicts of interest



  1. Abreu-Villaca Y, Seidler FJ, Slotkin TA (2003) Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific effects, regional selectivities, and the role of withdrawal. Brain Res 988:164–172. doi: 10.1016/S0006-8993(03)03368-7 PubMedCrossRefGoogle Scholar
  2. Adriani W, Granstrem O, Macri S, Izykenova G, Dambinova S, Laviola G (2004) Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine. Neuropsychopharmacology 29:869–878. doi: 10.1038/sj.npp.1300366 PubMedCrossRefGoogle Scholar
  3. Andersen SL (2003) Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev 27:3–18. doi: 10.1016/S0149-7634(03)00005-8 PubMedCrossRefGoogle Scholar
  4. Andersen SL, Dumont NL, Teicher MH (1997) Developmental differences in dopamine synthesis inhibition by (+/–)-7-OH-DPAT. Naunyn-Schmiedebergs Arch Pharmacol 356:173–181. doi: 10.1007/PL00005038 PubMedCrossRefGoogle Scholar
  5. Benoit-Marand M, Jaber M, Gonon F (2000) Release and elimination of dopamine in vivo in mice lacking the dopamine transporter: functional consequences. Eur J Neurosci 12:2985–2992. doi: 10.1046/j.1460-9568.2000.00155.x PubMedCrossRefGoogle Scholar
  6. Benwell ME, Balfour DJ, Birrell CE (1995) Desensitization of the nicotine-induced mesolimbic dopamine responses during constant infusion with nicotine. Br J Pharmacol 114:454–460PubMedGoogle Scholar
  7. Biederman J, Monuteaux MC, Mick E, Wilens TE, Fontanella JA, Poetzl KM, Kirk T, Masse J, Faraone SV (2006) Is cigarette smoking a gateway to alcohol and illicit drug use disorders? A study of youths with and without attention deficit hyperactivity disorder. Biol Psychiatry 59:258–264. doi: 10.1016/j.biopsych.2005.07.009 PubMedCrossRefGoogle Scholar
  8. Bobzean SA, Dennis TS, Addison BD, Perrotti LI (2010) Influence of sex on reinstatement of cocaine-conditioned place preference. Brain Res Bull. doi: 10.1016/j.brainresbull.2010.09.003 PubMedGoogle Scholar
  9. Boone EM, Hawks BW, Li W, Garlow SJ (2008) Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice. Brain Res 1194:1–7. doi: 10.1016/j.brainres.2007.11.074 PubMedCrossRefGoogle Scholar
  10. Bosy TZ, Ruth JA (1989) Differential inhibition of synaptosomal accumulation of [3H]-monoamines by cocaine, tropacocaine and amphetamine in four inbred strains of mice. Pharmacol Biochem Behav 34:165–172. doi: 10.1016/0091-3057(89)90368-7 PubMedCrossRefGoogle Scholar
  11. Cabib S, Orsini C, Le Moal M, Piazza PV (2000) Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience. Science 289:463–465. doi: 10.1126/science.289.5478.463 PubMedCrossRefGoogle Scholar
  12. Caine BS, Lintz R, Koob GF (1993) Intravenous drug self-administration techniques in animals. In: Sahgal A (ed) Behavioural neuroscience: a practical approach. Oxford University Press, Oxford, pp 117–143Google Scholar
  13. Chauvet C, Lardeux V, Goldberg SR, Jaber M, Solinas M (2009) Environmental enrichment reduces cocaine seeking and reinstatement induced by cues and stress but not by cocaine. Neuropsychopharmacology 34:2767–2778. doi: 10.1038/npp.2009.127 PubMedCrossRefGoogle Scholar
  14. Chesler EJ, Wang J, Lu L, Qu Y, Manly KF, Williams RW (2003) Genetic correlates of gene expression in recombinant inbred strains: a relational model system to explore neurobehavioral phenotypes. Neuroinformatics 1:343–357. doi: 10.1385/NI:1:4:343 PubMedCrossRefGoogle Scholar
  15. Collins SL, Izenwasser S (2004) Chronic nicotine differentially alters cocaine-induced locomotor activity in adolescent vs. adult male and female rats. Neuropharmacology 46:349–362. doi: 10.1016/j.neuropharm.2003.09.024 PubMedCrossRefGoogle Scholar
  16. Collins SL, Wade D, Ledon J, Izenwasser S (2004) Neurochemical alterations produced by daily nicotine exposure in periadolescent vs. adult male rats. Eur J Pharmacol 502:75–85. doi: 10.1016/j.ejphar.2004.08.039 PubMedCrossRefGoogle Scholar
  17. Coulter CL, Happe HK, Murrin LC (1996) Postnatal development of the dopamine transporter: a quantitative autoradiographic study. Brain Res Dev Brain Res 92:172–181. doi: 10.1016/0165-3806(96)00004-1 PubMedCrossRefGoogle Scholar
  18. Counotte DS, Spijker S, Van de Burgwal LH, Hogenboom F, Schoffelmeer AN, De Vries TJ, Smit AB, Pattij T (2009) Long-lasting cognitive deficits resulting from adolescent nicotine exposure in rats. Neuropsychopharmacology 34:299–306. doi: 10.1038/npp.2008.96 PubMedCrossRefGoogle Scholar
  19. Crabbe JC, Belknap JK, Buck KJ (1994) Genetic animal models of alcohol and drug abuse. Science 264:1715–1723. doi: 10.1126/science.8209252 PubMedCrossRefGoogle Scholar
  20. Cunningham CL, Dickinson SD, Grahame NJ, Okorn DM, McMullin CS (1999) Genetic differences in cocaine-induced conditioned place preference in mice depend on conditioning trial duration. Psychopharmacology (Berl) 146:73–80. doi: 10.1007/s002130051090 CrossRefGoogle Scholar
  21. Di Chiara G, Bassareo V, Fenu S, De Luca MA, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D (2004) Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology 47(Suppl 1):227–241. doi: 10.1016/j.neuropharm.2004.06.032 PubMedGoogle Scholar
  22. Dugast C, Suaud-Chagny MF, Gonon F (1994) Continuous in vivo monitoring of evoked dopamine release in the rat nucleus accumbens by amperometry. Neuroscience 62:647–654. doi: 10.1016/0306-4522(94)90466-9 PubMedCrossRefGoogle Scholar
  23. Dwyer JB, McQuown SC, Leslie FM (2009) The dynamic effects of nicotine on the developing brain. Pharmacol Ther 122:125–139. doi: 10.1016/j.pharmthera.2009.02.003 PubMedCrossRefGoogle Scholar
  24. Fergusson DM, Horwood LJ (2000) Does cannabis use encourage other forms of illicit drug use? Addiction 95:505–520. doi: 10.1046/j.1360-0443.2000.9545053.x PubMedCrossRefGoogle Scholar
  25. Fergusson DM, Boden JM, Horwood LJ (2006) Cannabis use and other illicit drug use: testing the cannabis gateway hypothesis. Addiction 101:556–569. doi: 10.1111/j.1360-0443.2005.01322.x PubMedCrossRefGoogle Scholar
  26. Forster GL, Blaha CD (2003) Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat. Eur J Neurosci 17:751–762. doi: 10.1046/j.1460-9568.2003.02511.x PubMedCrossRefGoogle Scholar
  27. Giedd JN (2004) Structural magnetic resonance imaging of the adolescent brain. Ann N Y Acad Sci 1021:77–85. doi: 10.1196/annals.1308.009 PubMedCrossRefGoogle Scholar
  28. Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL (1999) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2:861–863. doi: 10.1038/13158 PubMedCrossRefGoogle Scholar
  29. Girault JA, Greengard P (2004) The neurobiology of dopamine signaling. Arch Neurol 61:641–644. doi: 10.1001/archneur.61.5.641 PubMedCrossRefGoogle Scholar
  30. Goldman D, Oroszi G, Ducci F (2005) The genetics of addictions: uncovering the genes. Nat Rev Genet 6:521–532. doi: 10.1038/nrg1635 PubMedCrossRefGoogle Scholar
  31. Golub A, Johnson BD (2002) Substance use progression and hard drug use in inner-city New York. In: Kandel DB (ed) Stages and pathways of drug involvement: examining the gateway hypothesis. Cambridge University Press, New York, pp 90–112CrossRefGoogle Scholar
  32. Grahame NJ, Cunningham CL (1995) Genetic differences in intravenous cocaine self-administration between C57BL/6J and DBA/2J mice. Psychopharmacology 122:281–291. doi: 10.1007/BF02246549 PubMedCrossRefGoogle Scholar
  33. Haile CN, Kosten TR, Kosten TA (2007) Genetics of dopamine and its contribution to cocaine addiction. Behav Genet 37:119–145. doi: 10.1007/s10519-006-9115-2 PubMedCrossRefGoogle Scholar
  34. Hanna EZ, Yi HY, Dufour MC, Whitmore CC (2001) The relationship of early-onset regular smoking to alcohol use, depression, illicit drug use, and other risky behaviors during early adolescence: results from the youth supplement to the Third National Health and Nutrition Examination Survey. J Subst Abuse 13:265–282. doi: 10.1016/S0899-3289(01)00077-3 PubMedCrossRefGoogle Scholar
  35. Hedner T, Lundborg P (1985) Development of dopamine autoreceptors in the postnatal rat brain. J Neural Transm 62:53–63. doi: 10.1007/BF01260415 PubMedCrossRefGoogle Scholar
  36. Humensky JL (2010) Are adolescents with high socioeconomic status more likely to engage in alcohol and illicit drug use in early adulthood? Subst Abuse Treat Prev Policy 5:19. doi: 10.1186/1747-597X-5-19 PubMedCrossRefGoogle Scholar
  37. Janowsky A, Mah C, Johnson RA, Cunningham CL, Phillips TJ, Crabbe JC, Eshleman AJ, Belknap JK (2001) Mapping genes that regulate density of dopamine transporters and correlated behaviors in recombinant inbred mice. J Pharmacol Exp Ther 298:634–643PubMedGoogle Scholar
  38. Jones BC, Tarantino LM, Rodriguez LA, Reed CL, McClearn GE, Plomin R, Erwin VG (1999) Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry. Pharmacogenetics 9:607–617PubMedCrossRefGoogle Scholar
  39. Kandel D (1975) Stages in adolescent involvement in drug use. Science 190:912–914. doi: 10.1126/science.1188374 PubMedCrossRefGoogle Scholar
  40. Kandel DB, Yamaguchi K (2002) Stages of drug involvement in the US population. In: Kandel DB (ed) Stages and pathways of drug involvement: examining the gateway hypothesis. Cambridge University Press, New York, pp 65–89CrossRefGoogle Scholar
  41. Kandel DB, Yamaguchi K, Chen K (1992) Stages of progression in drug involvement from adolescence to adulthood: further evidence for the gateway theory. J Stud Alcohol 53:447–457PubMedGoogle Scholar
  42. Kelley BM, Middaugh LD (1999) Periadolescent nicotine exposure reduces cocaine reward in adult mice. J Addict Dis 18:27–39. doi: 10.1300/J069v18n03_04 PubMedCrossRefGoogle Scholar
  43. Kelley BM, Rowan JD (2004) Long-term, low-level adolescent nicotine exposure produces dose-dependent changes in cocaine sensitivity and reward in adult mice. Int J Dev Neurosci 22:339–348. doi: 10.1016/j.ijdevneu.2004.04.002 PubMedCrossRefGoogle Scholar
  44. Kuzmin A, Johansson B (2000) Reinforcing and neurochemical effects of cocaine: differences among C57, DBA, and 129 mice. Pharmacol Biochem Behav 65:399–406. doi: 10.1016/S0091-3057(99)00211-7 PubMedCrossRefGoogle Scholar
  45. Lai S, Lai H, Page JB, McCoy CB (2000) The association between cigarette smoking and drug abuse in the United States. J Addict Dis 19:11–24. doi: 10.1300/J069v19n04_02 PubMedCrossRefGoogle Scholar
  46. Lee KH, Blaha CD, Harris BT, Cooper S, Hitti FL, Leiter JC, Roberts DW, Kim U (2006) Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus: potential mechanism of action in Parkinson's disease. Eur J Neurosci 23:1005–1014. doi: 10.1111/j.1460-9568.2006.04638.x PubMedCrossRefGoogle Scholar
  47. Lemstra M, Bennett NR, Neudorf C, Kunst A, Nannapaneni U, Warren LM, Kershaw T, Scott CR (2008) A meta-analysis of marijuana and alcohol use by socio-economic status in adolescents aged 10–15 years. Can J Public Health 99:172–177PubMedGoogle Scholar
  48. Lester DB, Miller AD, Pate TD, Blaha CD (2008) Midbrain acetylcholine and glutamate receptors modulate accumbal dopamine release. Neuroreport 19:991–995. doi: 10.1097/WNR.0b013e3283036e5e PubMedCrossRefGoogle Scholar
  49. Lester DB, Miller AD, Blaha CD (2009) Muscarinic receptor blockade in the ventral tegmental area attenuates cocaine enhancement of laterodorsal tegmentum stimulation-evoked accumbens dopamine efflux in the mouse. Synapse 64:216–223. doi: 10.1002/syn.20717 CrossRefGoogle Scholar
  50. Matta SG, Balfour DJ, Benowitz NL, Boyd RT, Buccafusco JJ, Caggiula AR, Craig CR, Collins AC, Damaj MI, Donny EC, Gardiner PS, Grady SR, Heberlein U, Leonard SS, Levin ED, Lukas RJ, Markou A, Marks MJ, McCallum SE, Parameswaran N, Perkins KA, Picciotto MR, Quik M, Rose JE, Rothenfluh A, Schafer WR, Stolerman IP, Tyndale RF, Wehner JM, Zirger JM (2007) Guidelines on nicotine dose selection for in vivo research. Psychopharmacology 190:269–319. doi: 10.1007/s00213-006-0441-0 PubMedCrossRefGoogle Scholar
  51. McQuown SC, Belluzzi JD, Leslie FM (2007) Low dose nicotine treatment during early adolescence increases subsequent cocaine reward. Neurotoxicol Teratol 29:66–73. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  52. Merrill JC, Kleber HD, Shwartz M, Liu H, Lewis SR (1999) Cigarettes, alcohol, marijuana, other risk behaviors, and American youth. Drug Alcohol Depend 56:205–212. doi: 10.1016/S0376-8716(99)00034-4 PubMedCrossRefGoogle Scholar
  53. Miller G (2010) The seductive allure of behavioral epigenetics. Science 329:24–27. doi: 10.1126/science.329.5987.24 PubMedCrossRefGoogle Scholar
  54. Mittleman G, Goldowitz D, Heck DH, Blaha CD (2008) Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia. Synapse 62:544–550. doi: 10.1002/syn.20525 PubMedCrossRefGoogle Scholar
  55. Morgan D, Grant KA, Gage HD, Mach RH, Kaplan JR, Prioleau O, Nader SH, Buchheimer N, Ehrenkaufer RL, Nader MA (2002) Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat Neurosci 5:169–174. doi: 10.1038/nn798 PubMedCrossRefGoogle Scholar
  56. Orsini C, Bonito-Oliva A, Conversi D, Cabib S (2005) Susceptibility to conditioned place preference induced by addictive drugs in mice of the C57BL/6 and DBA/2 inbred strains. Psychopharmacology 181:327–336. doi: 10.1007/s00213-005-2259-6 PubMedCrossRefGoogle Scholar
  57. Paus T, Zijdenbos A, Worsley K, Collins DL, Blumenthal J, Giedd JN, Rapoport JL, Evans AC (1999) Structural maturation of neural pathways in children and adolescents: in vivo study. Science 283:1908–1911. doi: 10.1126/science.283.5409.1908 PubMedCrossRefGoogle Scholar
  58. Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates. Academic Press, San DiegoGoogle Scholar
  59. Peirce JL, Lu L, Gu J, Silver LM, Williams RW (2004) A new set of BXD recombinant inbred lines from advanced intercross populations in mice. BMC Genet 5:7. doi: 10.1186/1471-2156-5-7 PubMedCrossRefGoogle Scholar
  60. Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ (2010) High-throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strains. Genes Brain Behav 9:129–159. doi: 10.1111/j.1601-183X.2009.00540.x PubMedCrossRefGoogle Scholar
  61. Plomin R, McClearn GE, Gora-Maslak G, Neiderhiser JM (1991) Use of recombinant inbred strains to detect quantitative trait loci associated with behavior. Behav Genet 21:99–116. doi: 10.1007/BF01066330 PubMedCrossRefGoogle Scholar
  62. Puglisi-Allegra S, Cabib S (1997) Psychopharmacology of dopamine: the contribution of comparative studies in inbred strains of mice. Prog Neurobiol 51:637–661. doi: 10.1016/S0301-0082(97)00008-7 PubMedCrossRefGoogle Scholar
  63. Roberts A, Pardo-Manuel de Villena F, Wang W, McMillan L, Threadgill DW (2007) The polymorphism architecture of mouse genetic resources elucidated using genome-wide resequencing data: implications for QTL discovery and systems genetics. Mamm Genome 18:473–481. doi: 10.1007/s00335-007-9045-1 PubMedCrossRefGoogle Scholar
  64. Rocha BA, Odom LA, Barron BA, Ator R, Wild SA, Forster MJ (1998) Differential responsiveness to cocaine in C57BL/6J and DBA/2J mice. Psychopharmacology 138:82–88. doi: 10.1007/s002130050648 PubMedCrossRefGoogle Scholar
  65. Schönfuß D, Reum T, Olshausen P, Fischer T, Morgenstern R (2001) Modelling constant potential amperometry for investigations of dopaminergic neurotransmission kinetics in vivo. J Neurosci Methods 112:163–172. doi: 10.1016/S0165-0270(01)00465-4 PubMedCrossRefGoogle Scholar
  66. Seale TW, Carney JM (1991) Genetic determinants of susceptibility to the rewarding and other behavioral actions of cocaine. J Addict Dis 10:141–162. doi: 10.1300/J069v10n01_10 PubMedCrossRefGoogle Scholar
  67. Siu EC, Tyndale RF (2007) Characterization and comparison of nicotine and cotinine metabolism in vitro and in vivo in DBA/2 and C57BL/6 mice. Mol Pharmacol 71:826–834. doi: 10.1124/mol.106.032086 PubMedCrossRefGoogle Scholar
  68. Slotkin TA, MacKillop EA, Rudder CL, Ryde IT, Tate CA, Seidler FJ (2007) Permanent, sex-selective effects of prenatal or adolescent nicotine exposure, separately or sequentially, in rat brain regions: indices of cholinergic and serotonergic synaptic function, cell signaling, and neural cell number and size at 6 months of age. Neuropsychopharmacology 32:1082–1097. doi: 10.1038/sj.npp.1301231 PubMedCrossRefGoogle Scholar
  69. Smith MA, Iordanou JC, Cohen MB, Cole KT, Gergans SR, Lyle MA, Schmidt KT (2009) Effects of environmental enrichment on sensitivity to cocaine in female rats: importance of control rates of behavior. Behav Pharmacol 20:312–321. doi: 10.1097/FBP.0b013e32832ec568 PubMedCrossRefGoogle Scholar
  70. Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463. doi: 10.1016/S0149-7634(00)00014-2 PubMedCrossRefGoogle Scholar
  71. Suaud-Chagny MF (2004) In vivo monitoring of dopamine overflow in the central nervous system by amperometric techniques combined with carbon fibre electrodes. Methods 33:322–329. doi: 10.1016/j.ymeth.2004.01.009 PubMedCrossRefGoogle Scholar
  72. Tarazi FI, Baldessarini RJ (2000) Comparative postnatal development of dopamine D(1), D(2) and D(4) receptors in rat forebrain. Int J Dev Neurosci 18:29–37. doi: 10.1016/S0736-5748(99)00108-2 PubMedCrossRefGoogle Scholar
  73. Tarazi FI, Tomasini EC, Baldessarini RJ (1998) Postnatal development of dopamine and serotonin transporters in rat caudate–putamen and nucleus accumbens septi. Neurosci Lett 254:21–24. doi: 10.1016/S0304-3940(98)00644-2 PubMedCrossRefGoogle Scholar
  74. Taylor BA, Bedigian HG, Meier H (1977) Genetic studies of the Fv-1 locus of mice: linkage with Gpd-1 in recombinant inbred lines. J Virol 23:106–109PubMedGoogle Scholar
  75. Taylor BA, Wnek C, Kotlus BS, Roemer N, MacTaggart T, Phillips SJ (1999) Genotyping new BXD recombinant inbred mouse strains and comparison of BXD and consensus maps. Mamm Genome 10:335–348. doi: 10.1007/s003359900998 PubMedCrossRefGoogle Scholar
  76. Thiel KJ, Engelhardt B, Hood LE, Peartree NA, Neisewander JL (2010) The interactive effects of environmental enrichment and extinction interventions in attenuating cue-elicited cocaine-seeking behavior in rats. Pharmacol Biochem Behav 97:595–602. doi: 10.1016/j.pbb.2010.09.014 Google Scholar
  77. Tolliver BK, Carney JM (1994) Comparison of cocaine and GBR 12935: effects on locomotor activity and stereotypy in two inbred mouse strains. Pharmacol Biochem Behav 48:733–739. doi: 10.1016/0091-3057(94)90340-9 PubMedCrossRefGoogle Scholar
  78. Tolliver BK, Belknap JK, Woods WE, Carney JM (1994) Genetic analysis of sensitization and tolerance to cocaine. J Pharmacol Exp Ther 270:1230–1238PubMedGoogle Scholar
  79. Torabi MR, Bailey WJ, Majd-Jabbari M (1993) Cigarette smoking as a predictor of alcohol and other drug use by children and adolescents: evidence of the "gateway drug effect". J Sch Health 63:302–306. doi: 10.1111/j.1746-1561.1993.tb06150.x PubMedCrossRefGoogle Scholar
  80. Trauth JA, Seidler FJ, McCook EC, Slotkin TA (1999) Adolescent nicotine exposure causes persistent upregulation of nicotinic cholinergic receptors in rat brain regions. Brain Res 851:9–19. doi: 10.1016/S0006-8993(99)01994-0 PubMedCrossRefGoogle Scholar
  81. Trauth JA, Seidler FJ, Ali SF, Slotkin TA (2001) Adolescent nicotine exposure produces immediate and long-term changes in CNS noradrenergic and dopaminergic function. Brain Res 892:269–280. doi: 10.1016/S0006-8993(00)03227-3 PubMedCrossRefGoogle Scholar
  82. van der Veen R, Piazza PV, Deroche-Gamonet V (2007) Gene–environment interactions in vulnerability to cocaine intravenous self-administration: a brief social experience affects intake in DBA/2J but not in C57BL/6J mice. Psychopharmacology 193:179–186. doi: 10.1007/s00213-007-0777-0 PubMedCrossRefGoogle Scholar
  83. van der Veen R, Koehl M, Abrous DN, de Kloet ER, Piazza PV, Deroche-Gamonet V (2008) Maternal environment influences cocaine intake in adulthood in a genotype-dependent manner. PLoS One 3:e2245. doi: 10.1371/journal.pone.0002245 PubMedCrossRefGoogle Scholar
  84. Vansickel AR, Stoops WW, Rush CR (2010) Human sex differences in d-amphetamine self-administration. Addiction 105:727–731. doi: 10.1111/j.1360-0443.2009.02858.x PubMedCrossRefGoogle Scholar
  85. Wagner FA, Anthony JC (2002) Into the world of illegal drug use: exposure opportunity and other mechanisms linking the use of alcohol, tobacco, marijuana, and cocaine. Am J Epidemiol 155:918–925. doi: 10.1093/aje/155.10.918 PubMedCrossRefGoogle Scholar
  86. Williams RW, Gu J, Qi S, Lu L (2001) The genetic structure of recombinant inbred mice: high-resolution consensus maps for complex trait analysis. Genome Biol 2(11):RESEARCH0046. doi: 10.1186/gb-2001-2-11-research0046 PubMedCrossRefGoogle Scholar
  87. Womer DE, Jones BC, Erwin VG (1994) Characterization of dopamine transporter and locomotor effects of cocaine, GBR 12909, epidepride, and SCH 23390 in C57BL and DBA mice. Pharmacol Biochem Behav 48:327–335. doi: 10.1016/0091-3057(94)90534-7 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Price E. Dickson
    • 1
  • Tiffany D. Rogers
    • 1
  • Deranda B. Lester
    • 1
  • Mellessa M. Miller
    • 1
  • Shannon G. Matta
    • 2
  • Elissa J. Chesler
    • 3
  • Dan Goldowitz
    • 4
  • Charles D. Blaha
    • 1
  • Guy Mittleman
    • 1
  1. 1.Department of PsychologyUniversity of MemphisMemphisUSA
  2. 2.Department of Anatomy and NeurobiologyUniversity of Tennessee Health Science CenterMemphisUSA
  3. 3.The Jackson LaboratoryBar HarborUSA
  4. 4.Centre for Molecular Medicine and Therapeutics, Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada

Personalised recommendations