PT  - JOURNAL ARTICLE
AU  - Caine, S. Barak
AU  - Negus, S. Stevens
AU  - Mello, Nancy K.
AU  - Bergman, Jack
TI  - Effects of Dopamine D<sub>1-like</sub> and D<sub>2-like</sub>Agonists in Rats that Self-Administer Cocaine
DP  - 1999 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 353--360
VI  - 291
IP  - 1
4099  - http://jpet.aspetjournals.org/content/291/1/353.short
4100  - http://jpet.aspetjournals.org/content/291/1/353.full
SO  - J Pharmacol Exp Ther1999 Oct 01; 291
AB  - The reinforcing effects of D1-like and D2-likeagonists, and their capacity to modify cocaine self-administration, were compared in rats with extensive cocaine self-administration experience. Cocaine (0.01–1.0 mg i.v.) dose-dependently maintained responding under a fixed ratio (FR) 5 schedule of reinforcement, and an inverted U-shaped function characterized the relationship between unit dose and self-administration behavior. When substituted for cocaine, the D1-like agonists SKF 82958 (0.001–0.032 mg i.v.) and SKF 77434 (0.001–0.1 mg i.v.) did not maintain responding above levels observed during saline substitution. In contrast, the D2-like agonists quinelorane (0.001–0.1 mg i.v.) and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT; 0.01–0.32 mg i.v.) reliably maintained i.v. self-administration behavior that was characterized by inverted U-shaped dose-effect functions. Pretreatment with the D1-like agonists SKF 82958 and SKF 77434 (0.1–1.0 mg/kg i.p.) shifted the dose-effect function for cocaine self-administration downward, whereas pretreatment with the D2-like agonists quinelorane (0.01 mg/kg i.p.) and 7-OH-DPAT (0.32–1.0 mg/kg i.p.) shifted the cocaine dose-effect function to the left. Effects of D1-like and D2-like agonists on patterns of responding maintained by cocaine (0.32 mg i.v.) also differed: D1-like agonists increased the latency to the first response but did not otherwise alter patterns of cocaine self-administration, whereas D2-likeagonists increased the intervals between self-administered cocaine injections. The results suggest that D2-like agonists, but not D1-like agonists, have prominent reinforcing effects and enhance the effects of self-administered cocaine in rats with extensive cocaine self-administration experience. Consequently, D2 receptor-related neuronal mechanisms may be especially important in mediating the abuse-related effects of cocaine. The American Society for Pharmacology and Experimental Therapeutics