Psychopharmacology

, Volume 169, Issue 2, pp 161–168 | Cite as

Locomotor and discriminative-stimulus effects of cocaine in dopamine D5 receptor knockout mice

  • Elizabeth E. Elliot
  • David R. Sibley
  • Jonathan L. Katz
Original Investigation

Abstract

Rationale

Dopamine D1-like antagonists block several effects of cocaine, including its locomotor-stimulant and discriminative-stimulus effects. Because these compounds generally lack selectivity among the dopamine D1 and D5 receptors, the specific roles of the subtypes have not been determined.

Objectives

Dopamine D5 receptor knockout (DA D5R KO), heterozygous (HET) and wild-type (WT) mice were used to study the role of D5 dopamine receptors in the effects of cocaine. In addition, effects of the D1-like antagonist, SCH 39166 were also studied to further clarify the roles of D1 and D5 dopamine receptors in the discriminative-stimulus effects of cocaine.

Methods

DA D5R KO, HET and WT mice were treated with cocaine (3–30 mg/kg) or vehicle and their horizontal locomotor activity was assessed. The mice were also trained to discriminate IP injections of saline from cocaine (10 mg/kg) using a two-lever food-reinforcement (FR10) procedure. Doses of cocaine (1.0–10 mg/kg) were administered 5 min before 15-min test-sessions.

Results

Cocaine dose-dependently stimulated activity in each genotype, with the highest level of activity induced in the DA D5R WT mice. Both DA D5R KO and HET mice showed reduced levels of horizontal activity compared to WT mice. All three genotypes acquired the discrimination of 10 mg/kg cocaine; doses of 1.0–10.0 mg/kg produced dose-related increases in the number of cocaine-appropriate responses. SCH 39166, at inactive to fully active doses (0.01–0.1 mg/kg) produced predominately saline-appropriate responding. SCH 39166 produced a dose-dependent rightward shift in the cocaine dose-effect curve in all genotypes, with similar apparent affinities.

Conclusions

The present data suggest an involvement of DA D5R in the locomotor stimulant effects of cocaine. In addition, the data indicate that there is little involvement of the DA D5R in the discriminative-stimulus effects of cocaine. In addition, the antagonism data suggest a role of the D1 receptor in the behavioral effects of cocaine.

Keywords

Dopamine D5 Knockout Cocaine SCH 39166 Locomotor activity Drug discrimination 

Notes

Acknowledgements

The authors would like to thank Dawn French, Ben Nickle, and Patty Ballerstadt for technical and administrative support. The research was supported by funding by the National Institute on Drug Abuse Intramural Research Program (J.L.K.) and the National Institute of Neurological Disorders and Stroke (D.R.S.).

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Elizabeth E. Elliot
    • 1
  • David R. Sibley
    • 3
  • Jonathan L. Katz
    • 2
  1. 1.Department of Public HealthAdelaide UniversityAustralia
  2. 2.Psychobiology SectionNational Institute on Drug Abuse, National Institutes of HealthBethesdaUSA
  3. 3.Molecular Neuropharmacology SectionNational Institute of Neurological Disorders and Stroke, National Institutes of HealthBethesdaUSA

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