Selective D 1 and D 2 dopamine antagonists decrease response rates of food-maintained behavior and reduce the discriminative stimulus produced by heroin

Abstract

Animals were trained to discriminate heroin from saline in a two-lever food-reinforced paradigm. Tests with the heroin metabolites O 6-monoacetylmorphine and morphine suggest that the heroin discriminative stimulus was mediated by monoacetylmorphine. The heroin discriminative stimulus was not blocked by pretreatment with low doses of the D 1 dopamine antagonist SCH23390 or the D 2 antagonist spiperone; higher doses of the antagonists produced decreases both in selection of the drug-appropriate lever after heroin, and in food-maintained responding. The data suggest that dopamine may mediate the heroin discriminative stimulus. When administered in the absence of opioids, the D 2 antagonist spiperone did not have rate-decreasing effects, whereas SCH23390 did. Heroin partially reversed the rate-decreasing effects of SCH23390, possibly as a result of the ability of opioids to release dopamine.