Effects of dopamine D1-like and D2-like agonists in rats trained to discriminate cocaine from saline: influence of experimental history.

Effects of D1-like and D2-like agonists were compared in rats (Rattus norvegicus) with differing levels of experience (24 or 9 mo) in a cocaine discrimination procedure (5.6 mg/kg cocaine; fixed-ratio 20 schedule of food presentation). Cocaine, d-amphetamine, and D2-like agonists (quinelorane, 7-OH-DPAT) dose-dependently substituted for cocaine in both groups of rats. In contrast, D1-like agonists (SKF 82958, SKF 77434) substituted for cocaine only in rats with less discrimination experience. Pretreatment with D2-like agonists increased the stimulus effects of low cocaine-doses in both groups, whereas D1-like agonists produced these effects only in rats with less discrimination experience. The data suggest that the stimulus effects of cocaine overlap with those of D2-like agonists across a broader range of conditions than with those of D1-like agonists. Thus, D2-like receptors may play an especially important role in cocaine's behavioral effects.