Psychopharmacology

, 200:117

Comparison of dopamine D1 and D5 receptor knockout mice for cocaine locomotor sensitization

  • Rose-Marie Karlsson
  • Kathryn R. Hefner
  • David R. Sibley
  • Andrew Holmes
Original Investigation

Abstract

Rationale

There is compelling support for the contribution of dopamine and the D1R-like (D1R, D5R) receptor subfamily to the behavioral and neural effects of psychostimulant drugs of abuse. The relative roles of D1R and D5R subtypes in mediating these effects are not clear.

Objectives

The objectives of this study are to directly compare (C57BL/6J congenic) D1R knockout (KO) and D5R KO mice for baseline locomotor exploration, acute locomotor responses to cocaine, and locomotor sensitization to repeated cocaine administration, and to examine cocaine conditioned place preference (CPP) in D5R KO.

Materials and methods

D1R KO, D5R KO, and wild-type (WT) were assessed for baseline open field exploration, locomotor-stimulating effects of 15 mg/kg acute cocaine and sensitized locomotor responses to cocaine after repeated home cage treatment with 20 or 30 mg/kg cocaine. D5R KO and WT were tested for CPP to 15 mg/kg cocaine.

Results

D1R KO showed modest basal hyperactivity and increased center exploration relative to WT. Acute locomotor responses to cocaine were consistently absent in D1R KO, but intact in D5R KO. D5R KO showed normal locomotor sensitization to cocaine and normal cocaine CPP. D1R KO failed to show a sensitized locomotor response to 30 mg/kg cocaine. Failure to sensitize in D1R KO was not because of excessive stereotypies. Surprisingly, D1R KO showed a strong trend for sensitization to 20 mg/kg cocaine.

Conclusions

D5R KO does not alter acute or sensitized locomotor responses to cocaine or cocaine CPP. D1R KO abolishes acute locomotor response to cocaine, but does not fully prevent locomotor sensitization to cocaine at all doses.

Keywords

Dopamine Cocaine Knockout Mouse Psychostimulant Addiction Locomotor Reward Open field Conditioned place preference Receptor 

References

  1. Baker DA, Fuchs RA, Specio SE, Khroyan TV, Neisewander JL (1998) Effects of intraaccumbens administration of SCH-23390 on cocaine-induced locomotion and conditioned place preference. Synapse 30:181–193PubMedCrossRefGoogle Scholar
  2. Barrett AC, Miller JR, Dohrmann JM, Caine SB (2004) Effects of dopamine indirect agonists and selective D1-like and D2-like agonists and antagonists on cocaine self-administration and food maintained responding in rats. Neuropharmacology 47(Suppl 1):256–273PubMedCrossRefGoogle Scholar
  3. Bergson C, Mrzljak L, Smiley JF, Pappy M, Levenson R, Goldman-Rakic PS (1995) Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain. J Neurosci 15:7821–7836PubMedGoogle Scholar
  4. Beurrier C, Malenka RC (2002) Enhanced inhibition of synaptic transmission by dopamine in the nucleus accumbens during behavioral sensitization to cocaine. J Neurosci 22:5817–5822PubMedGoogle Scholar
  5. Boyce-Rustay JM, Holmes A (2006) Ethanol-related behaviors in mice lacking the NMDA receptor NR2A subunit. Psychopharmacology (Berl) 187:455–466CrossRefGoogle Scholar
  6. Boyce-Rustay JM, Wiedholz LM, Millstein RA, Carroll J, Murphy DL, Daws LC, Holmes A (2006) Ethanol-related behaviors in serotonin transporter knockout mice. Alcohol Clin Exp Res 30:1957–1965PubMedCrossRefGoogle Scholar
  7. Cabib S, Castellano C, Cestari V, Filibeck U, Puglisi-Allegra S (1991) D1 and D2 receptor antagonists differently affect cocaine-induced locomotor hyperactivity in the mouse. Psychopharmacology (Berl) 105:335–339CrossRefGoogle Scholar
  8. Centonze D, Grande C, Saulle E, Martin AB, Gubellini P, Pavon N, Pisani A, Bernardi G, Moratalla R, Calabresi P (2003) Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity. J Neurosci 23:8506–8512PubMedGoogle Scholar
  9. Cervo L, Samanin R (1995) Effects of dopaminergic and glutamatergic receptor antagonists on the acquisition and expression of cocaine conditioning place preference. Brain Res 673:242–250PubMedCrossRefGoogle Scholar
  10. Chen R, Zhang M, Park S, Gnegy ME (2007) C57BL/6J mice show greater amphetamine-induced locomotor activation and dopamine efflux in the striatum than 129S2/SvHsd mice. Pharmacol Biochem Behav 87(1):158–163PubMedCrossRefGoogle Scholar
  11. Ciliax BJ, Nash N, Heilman C, Sunahara R, Hartney A, Tiberi M, Rye DB, Caron MG, Niznik HB, Levey AI (2000) Dopamine D(5) receptor immunolocalization in rat and monkey brain. Synapse 37:125–145PubMedCrossRefGoogle Scholar
  12. Corvol JC, Valjent E, Pascoli V, Robin A, Stipanovich A, Luedtke RR, Belluscio L, Girault JA, Herve D (2007) Quantitative changes in Galphaolf protein levels, but not D1 receptor, alter specifically acute responses to psychostimulants. Neuropsychopharmacology 32:1109–1121PubMedCrossRefGoogle Scholar
  13. Crawford CA, Drago J, Watson JB, Levine MS (1997) Effects of repeated amphetamine treatment on the locomotor activity of the dopamine D1A-deficient mouse. Neuroreport 8:2523–2527PubMedCrossRefGoogle Scholar
  14. Creese I, Iversen SD (1974) The role of forebrain dopamine systems in amphetamine induced stereotyped behavior in the rat. Psychopharmacologia 39:345–357PubMedCrossRefGoogle Scholar
  15. Daunais JB, McGinty JF (1994) Acute and chronic cocaine administration differentially alters striatal opioid and nuclear transcription factor mRNAs. Synapse 18:35–45PubMedCrossRefGoogle Scholar
  16. Drago J, Gerfen CR, Lachowicz JE, Steiner H, Hollon TR, Love PE, Ooi GT, Grinberg A, Lee EJ, Huang SP et al (1994) Altered striatal function in a mutant mouse lacking D1A dopamine receptors. Proc Natl Acad Sci USA 91:12564–12568PubMedCrossRefGoogle Scholar
  17. Drago J, Gerfen CR, Westphal H, Steiner H (1996) D1 dopamine receptor-deficient mouse: cocaine-induced regulation of immediate-early gene and substance P expression in the striatum. Neuroscience 74:813–823PubMedCrossRefGoogle Scholar
  18. Elliot EE, Sibley DR, Katz JL (2003) Locomotor and discriminative-stimulus effects of cocaine in dopamine D5 receptor knockout mice. Psychopharmacology (Berl) 169:161–168CrossRefGoogle Scholar
  19. Everitt BJ, Wolf ME (2002) Psychomotor stimulant addiction: a neural systems perspective. J Neurosci 22:3312–3320PubMedGoogle Scholar
  20. Fontana D, Post RM, Weiss SR, Pert A (1993) The role of D1 and D2 dopamine receptors in the acquisition and expression of cocaine-induced conditioned increases in locomotor behavior. Behav Pharmacol 4:375–387PubMedCrossRefGoogle Scholar
  21. Grandy DK, Zhang YA, Bouvier C, Zhou QY, Johnson RA, Allen L, Buck K, Bunzow JR, Salon J, Civelli O (1991) Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes. Proc Natl Acad Sci USA 88:9175–9179PubMedCrossRefGoogle Scholar
  22. Hefner K, Holmes A (2007) An investigation of the behavioral actions of ethanol across adolescence in mice. Psychopharmacology (Berl) 191:311–322CrossRefGoogle Scholar
  23. Henry DJ, White FJ (1991) Repeated cocaine administration causes persistent enhancement of D1 dopamine receptor sensitivity within the rat nucleus accumbens. J Pharmacol Exp Ther 258:882–890PubMedGoogle Scholar
  24. Henry DJ, White FJ (1995) The persistence of behavioral sensitization to cocaine parallels enhanced inhibition of nucleus accumbens neurons. J Neurosci 15:6287–6299PubMedGoogle Scholar
  25. Heusner CL, Palmiter RD (2005) Expression of mutant NMDA receptors in dopamine D1 receptor-containing cells prevents cocaine sensitization and decreases cocaine preference. J Neurosci 25:6651–6657PubMedCrossRefGoogle Scholar
  26. Hnasko TS, Sotak BN, Palmiter RD (2007) Cocaine-conditioned place preference by dopamine-deficient mice is mediated by serotonin. J Neurosci 27:12484–12488PubMedCrossRefGoogle Scholar
  27. Hollon TR, Bek MJ, Lachowicz JE, Ariano MA, Mezey E, Ramachandran R, Wersinger SR, Soares-da-Silva P, Liu ZF, Grinberg A, Drago J, Young WS 3rd, Westphal H, Jose PA, Sibley DR (2002) Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci 22:10801–10810PubMedGoogle Scholar
  28. Holmes A, Hollon TR, Gleason TC, Liu Z, Dreiling J, Sibley DR, Crawley JN (2001) Behavioral characterization of dopamine D5 receptor null mutant mice. Behav Neurosci 115:1129–1144PubMedCrossRefGoogle Scholar
  29. Holmes A, Li Q, Murphy DL, Gold E, Crawley JN (2003) Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the influence of genetic background. Genes Brain Behav 2:365–380PubMedCrossRefGoogle Scholar
  30. Holmes A, Lachowicz JE, Sibley DR (2004) Phenotypic analysis of dopamine receptor knockout mice; recent insights into the functional specificity of dopamine receptor subtypes. Neuropharmacology 47:1117–1134PubMedGoogle Scholar
  31. Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Brain Res Rev 16:223–244PubMedCrossRefGoogle Scholar
  32. Karasinska JM, George SR, Cheng R, O’Dowd BF (2005) Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation. Eur J Neurosci 22:1741–1750PubMedCrossRefGoogle Scholar
  33. Karper PE, De la Rosa H, Newman ER, Krall CM, Nazarian A, McDougall SA, Crawford CA (2002) Role of D1-like receptors in amphetamine-induced behavioral sensitization: a study using D1A receptor knockout mice. Psychopharmacology (Berl) 159:407–414CrossRefGoogle Scholar
  34. Kelly MA, Rubinstein M, Phillips TJ, Lessov CN, Burkhart-Kasch S, Zhang G, Bunzow JR, Fang Y, Gerhardt GA, Grandy DK, Low MJ (1998) Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene dosage, genetic background, and developmental adaptations. J Neurosci 18:3470–3479PubMedGoogle Scholar
  35. Khan ZU, Gutierrez A, Martin R, Penafiel A, Rivera A, de la Calle A (2000) Dopamine D5 receptors of rat and human brain. Neuroscience 100:689–699PubMedCrossRefGoogle Scholar
  36. Lachowicz JE, Sibley DR (1997) Molecular characteristics of mammalian dopamine receptors. Pharmacol Toxicol 81:105–113PubMedCrossRefGoogle Scholar
  37. Mattingly BA, Rowlett JK, Ellison T, Rase K (1996) Cocaine-induced behavioral sensitization: effects of haloperidol and SCH 23390 treatments. Pharmacol Biochem Behav 53:481–486PubMedCrossRefGoogle Scholar
  38. McCreary AC, Marsden CA (1993) Cocaine-induced behaviour: dopamine D1 receptor antagonism by SCH 23390 prevents expression of conditioned sensitisation following repeated administration of cocaine. Neuropharmacology 32:387–391PubMedCrossRefGoogle Scholar
  39. McDougall SA, Reichel CM, Cyr MC, Karper PE, Nazarian A, Crawford CA (2005) Importance of D(1) receptors for associative components of amphetamine-induced behavioral sensitization and conditioned activity: a study using D(1) receptor knockout mice. Psychopharmacology (Berl) 183:20–30CrossRefGoogle Scholar
  40. Millstein RA, Holmes A (2007) Effects of repeated maternal separation on anxiety- and depression-related phenotypes in different mouse strains. Neurosci Biobehav Rev 31:3–17PubMedCrossRefGoogle Scholar
  41. Miner LL, Drago J, Chamberlain PM, Donovan D, Uhl GR (1995) Retained cocaine conditioned place preference in D1 receptor deficient mice. Neuroreport 6:2314–2316PubMedCrossRefGoogle Scholar
  42. O’Sullivan GJ, Kinsella A, Sibley DR, Tighe O, Croke DT, Waddington JL (2005) Ethological resolution of behavioural topography and D1-like versus D2-like agonist responses in congenic D5 dopamine receptor mutants: identification of D5:D2-like interactions. Synapse 55:201–211PubMedCrossRefGoogle Scholar
  43. Phillips TJ (1997) Behavior genetics of drug sensitization. Crit Rev Neurobiol 11:21–33PubMedGoogle Scholar
  44. Pierce RC, Kumaresan V (2006) The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 30:215–238PubMedCrossRefGoogle Scholar
  45. Post RM, Rose H (1976) Increasing effects of repetitive cocaine administration in the rat. Nature 260:731–732PubMedCrossRefGoogle Scholar
  46. Pruitt DL, Bolanos CA, McDougall SA (1995) Effects of dopamine D1 and D2 receptor antagonists on cocaine-induced place preference conditioning in preweaning rats. Eur J Pharmacol 283:125–131PubMedCrossRefGoogle Scholar
  47. Robinson TE, Berridge KC (2003) Addiction. Annu Rev Psychol 54:25–53PubMedCrossRefGoogle Scholar
  48. Romach MK, Glue P, Kampman K, Kaplan HL, Somer GR, Poole S, Clarke L, Coffin V, Cornish J, O’Brien CP, Sellers EM (1999) Attenuation of the euphoric effects of cocaine by the dopamine D1/D5 antagonist ecopipam (SCH 39166). Arch Gen Psychiatry 56:1101–1106PubMedCrossRefGoogle Scholar
  49. Schilstrom B, Yaka R, Argilli E, Suvarna N, Schumann J, Chen BT, Carman M, Singh V, Mailliard WS, Ron D, Bonci A (2006) Cocaine enhances NMDA receptor-mediated currents in ventral tegmental area cells via dopamine D5 receptor-dependent redistribution of NMDA receptors. J Neurosci 26:8549–8558PubMedCrossRefGoogle Scholar
  50. Schlussman SD, Zhang Y, Kane S, Stewart CL, Ho A, Kreek MJ (2003) Locomotion, stereotypy, and dopamine D1 receptors after chronic “binge” cocaine in C57BL/6J and 129/J mice. Pharmacol Biochem Behav 75:123–131PubMedCrossRefGoogle Scholar
  51. Self DW (2004) Regulation of drug-taking and -seeking behaviors by neuroadaptations in the mesolimbic dopamine system. Neuropharmacology 47(Suppl 1):242–255PubMedCrossRefGoogle Scholar
  52. Sibley DR (1999) New insights into dopaminergic receptor function using antisense and genetically altered animals. Annu Rev Pharmacol Toxicol 39:313–341PubMedCrossRefGoogle Scholar
  53. Stanwood GD, Parlaman JP, Levitt P (2005) Anatomical abnormalities in dopaminoceptive regions of the cerebral cortex of dopamine D1 receptor mutant mice. J Comp Neurol 487:270–282PubMedCrossRefGoogle Scholar
  54. Stanwood GD, Parlaman JP, Levitt P (2006) Genetic or pharmacological inactivation of the dopamine D1 receptor differentially alters the expression of regulator of G-protein signalling (Rgs) transcripts. Eur J Neurosci 24:806–818PubMedCrossRefGoogle Scholar
  55. Steketee JD (1998) Injection of SCH 23390 into the ventral tegmental area blocks the development of neurochemical but not behavioral sensitization to cocaine. Behav Pharmacol 9:69–76PubMedGoogle Scholar
  56. Surmeier DJ, Song WJ, Yan Z (1996) Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J Neurosci 16:6579–6591PubMedGoogle Scholar
  57. Svenningsson P, Tzavara ET, Carruthers R, Rachleff I, Wattler S, Nehls M, McKinzie DL, Fienberg AA, Nomikos GG, Greengard P (2003) Diverse psychotomimetics act through a common signaling pathway. Science 302:1412–1415PubMedCrossRefGoogle Scholar
  58. Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau RT Jr, Caron MG (1991) Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor. Proc Natl Acad Sci USA 88:7491–7495PubMedCrossRefGoogle Scholar
  59. Tzschentke TM (2007) Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12:227–462PubMedCrossRefGoogle Scholar
  60. Waddington JL, O’Tuathaigh C, O’Sullivan G, Tomiyama K, Koshikawa N, Croke DT (2005) Phenotypic studies on dopamine receptor subtype and associated signal transduction mutants: insights and challenges from 10 years at the psychopharmacology-molecular biology interface. Psychopharmacology (Berl) 181:611–638CrossRefGoogle Scholar
  61. White FJ, Joshi A, Koeltzow TE, Hu XT (1998) Dopamine receptor antagonists fail to prevent induction of cocaine sensitization. Neuropsychopharmacology 18:26–40PubMedCrossRefGoogle Scholar
  62. Wolfer DP, Crusio WE, Lipp HP (2002) Knockout mice: simple solutions to the problems of genetic background and flanking genes. Trends Neurosci 25:336–340PubMedCrossRefGoogle Scholar
  63. Xu M, Hu XT, Cooper DC, Moratalla R, Graybiel AM, White FJ, Tonegawa S (1994) Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine D1 receptor mutant mice. Cell 79:945–955PubMedCrossRefGoogle Scholar
  64. Xu M, Guo Y, Vorhees CV, Zhang J (2000) Behavioral responses to cocaine and amphetamine administration in mice lacking the dopamine D1 receptor. Brain Res 852:198–207PubMedCrossRefGoogle Scholar
  65. Zhang D, Zhang L, Tang Y, Zhang Q, Lou D, Sharp FR, Zhang J, Xu M (2005) Repeated cocaine administration induces gene expression changes through the dopamine D1 receptors. Neuropsychopharmacology 30:1443–1454PubMedCrossRefGoogle Scholar
  66. Zhang J, Zhang L, Jiao H, Zhang Q, Zhang D, Lou D, Katz JL, Xu M (2006) c-Fos facilitates the acquisition and extinction of cocaine-induced persistent changes. J Neurosci 26:13287–13296PubMedCrossRefGoogle Scholar

Copyright information

© US Government 2008

Authors and Affiliations

  • Rose-Marie Karlsson
    • 1
  • Kathryn R. Hefner
    • 1
  • David R. Sibley
    • 2
  • Andrew Holmes
    • 1
  1. 1.Section on Behavioral Science and Genetics, Laboratory for Integrative NeuroscienceNational Institute on Alcohol Abuse and AlcoholismRockvilleUSA
  2. 2.Molecular Neuropharmacology Section, National Institute of Neurological Disease and StrokeNational Institute of Mental HealthBethesdaUSA

Personalised recommendations