, Volume 122, Issue 3, pp 209–214 | Cite as

Chromosomal mapping of the psychomotor stimulant effects of cocaine in BXD recombinant inbred mice

  • L. L. Miner
  • R. J. Marley
Original Investigation


To elucidate genes associated with cocaine's locomotor stimulant effects, we used recombinant inbred-quantitative trait loci (RI-QTL) analyses to identify chromosomal loci associated with locomotor activity before (baseline) and after cocaine treatment. RI-QTL analyses seek to identify associations between a quantitative measure of a phenotype and one or more previously mapped marker loci across a panel of RI strains. In the present study, 11 BXD RI strains were used to identify several putative QTLs for each phenotype. Both baseline locomotor activity and cocaine's locomotor stimulant effects are polygenic, with both unique and overlapping genetic influences. The largest associations for baseline activity were observed on chromosomes 5 and 9 and the largest associations for cocaine's psychomotor stimulant effects on chromosomes 3 and 17.

Key words

Cocaine Chromosomal mapping Psychostimulant effects recombinant inbred mice 


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  1. Carroll ME, Lac ST, Asenio M, Kragh R (1990) Fluoxetine reduces intravenous cocaine self-administration in rats. Pharmacol Biochem Behav 35: 237–244Google Scholar
  2. Cohen P (1990) Desires for cocaine. In: Warburton DM (ed) Addiction controversies. Chur: Harwood 212–222Google Scholar
  3. Copeland NG, Jenkins NA, Gilbert DJ, Eppig JT, Maltais LJ, Miller JC, Dietrich WF, Weaver A, Lincoln SE, Steen RG, Stein LD, Nadeau JH, Lander ES (1993) A genetic linkage map of the mouse: current applications and future prospects. Science 262: 57–66Google Scholar
  4. Costall B, Naylor RJ (1992) Serotonin and psychiatric disorders: a key to new therapeutic approaches. Arzneimittelforschung 42: 246–249Google Scholar
  5. Crabbe, JC, Belknap JK, Buck KJ (1994) Genetic animal models of alcohol and drug abuse. Science 264: 1715–1723Google Scholar
  6. De Wit J, Uhlenhuth EH, Johanson CE (1986) Individual differences in the reinforcing and subjective effects of amphetamine and diazepam. Drug Alcohol Depend 16: 341–360Google Scholar
  7. George FR, Porrino LJ, Ritz MC, Goldberg SR (1991) Inbred rat strain comparisons indicate different sites of action for cocaine and amphetamine locomotor stimulant effects. Psychopharmacology 104: 457–462Google Scholar
  8. Gora-Maslak G, McClearn GE, Crabbe JC, Phillips TJ, Belknap JK, Plomin R (1991) Use of recombinant inbred strains to identify quantitative trait loci in psychopharmacology. Psychopharmacology 104: 413–424Google Scholar
  9. Guitart X, Beitner-Johnson D, Marby DW, Kosten TA, Nestler EJ (1992) Fisher and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system. Synapse 12: 242–253Google Scholar
  10. Le Moal M, Simon H (1991) Mesocortical dopaminergic network: functional and regulator roles. Physiol Rev 71: 155–234Google Scholar
  11. Lossie AC, Vandenbergh DJ, Camper SA (1994) Localization of the dopamine transporter gene, Dat1, on mouse chromosome 13. Mammalian Genome 5: 117–118Google Scholar
  12. Maltais LJ, Doolittle DP, Roderick TH, Hillyard AL, Davisson MT (1994) Locus map of mouse. Mouse Genome 92: 62–85Google Scholar
  13. Marley RJ, Witkin JM, Goldberg SR (1991a) Genetic factors influence changes in sensitivity to the convulsant properties of cocaine following chronic treatment. Brain Res 542: 1–7Google Scholar
  14. Marley RJ, Witkin JM, Goldberg SR (1991b) A pharmacogenetic evaluation of the role of local anesthetic actions in the cocaine kindling process. Brain Res 562: 251–257Google Scholar
  15. Miner LL, Marley RJ (1995) Chromosomal mapping of loci influencing sensitivity to cocaine-induced seizures in BXD recombinant inbred strains of mice. Psychopharmacology 117: 62–66Google Scholar
  16. Porrino LJ, Ritz MC, Goodman NL, Sharpe LG, Kuhar MJ, Goldberg SR (1988) Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats. Life Sci 45: 1529–1535Google Scholar
  17. Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237: 1219–1223Google Scholar
  18. Ruth JA, Ullman EA, Collins AC (1988) An analysis of cocaine effects on locomotor activities and heart rate in four inbred mouse strains. Pharmacol Biochem Behav 29: 157–162Google Scholar
  19. Schechter MD (1992) Rats bred for differences in preference to cocaine: other behavioral measurements. Pharmacol Biochem Behav 43: 1015–1021Google Scholar
  20. Shuster L, Yu G, Bates A (1977) Sensitization to cocaine stimulation in mice. Psychopharmacology 52: 185–190Google Scholar
  21. Silverman BW (1986) Density estimates for statistics and data analysis. Chapman and Hall, LondonGoogle Scholar
  22. Tolliver BK, Belknap JK, Woods WE, Carney JM (1994) Genetic analysis of sensitization and tolerance to cocaine. J Pharmacol Exp Ther 270: 1230–1238Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • L. L. Miner
    • 1
    • 2
  • R. J. Marley
    • 2
  1. 1.Molecular Neurobiology Branch, NIDA/ARCBaltimoreUSA
  2. 2.Genetics Section, Molecular Neurobiology Branch, Division of Intramural Research, Addiction Research CenterNational Institute on Drug AbuseBaltimoreUSA

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