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Locomotor and discriminative-stimulus effects of cocaine in dopamine D5 receptor knockout mice.
Psychopharmacology (Berl). 2003 Sep; 169(2):161-8.P

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.

Authors+Show Affiliations

Department of Public Health, Adelaide University, 5005 South Australia, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12768268

Citation

Elliot, Elizabeth E., et al. "Locomotor and Discriminative-stimulus Effects of Cocaine in Dopamine D5 Receptor Knockout Mice." Psychopharmacology, vol. 169, no. 2, 2003, pp. 161-8.
Elliot EE, Sibley DR, Katz JL. Locomotor and discriminative-stimulus effects of cocaine in dopamine D5 receptor knockout mice. Psychopharmacology (Berl). 2003;169(2):161-8.
Elliot, E. E., Sibley, D. R., & Katz, J. L. (2003). Locomotor and discriminative-stimulus effects of cocaine in dopamine D5 receptor knockout mice. Psychopharmacology, 169(2), 161-8.
Elliot EE, Sibley DR, Katz JL. Locomotor and Discriminative-stimulus Effects of Cocaine in Dopamine D5 Receptor Knockout Mice. Psychopharmacology (Berl). 2003;169(2):161-8. PubMed PMID: 12768268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Locomotor and discriminative-stimulus effects of cocaine in dopamine D5 receptor knockout mice. AU - Elliot,Elizabeth E, AU - Sibley,David R, AU - Katz,Jonathan L, Y1 - 2003/05/27/ PY - 2002/09/08/received PY - 2003/03/25/accepted PY - 2003/5/28/pubmed PY - 2004/2/11/medline PY - 2003/5/28/entrez SP - 161 EP - 8 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 169 IS - 2 N2 - 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/12768268/Locomotor_and_discriminative_stimulus_effects_of_cocaine_in_dopamine_D5_receptor_knockout_mice_ L2 - https://dx.doi.org/10.1007/s00213-003-1494-y DB - PRIME DP - Unbound Medicine ER -