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Animals were trained to discriminate heroin from saline in a two-lever food-reinforced paradigm. Tests with the heroin metabolites O6-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 D1 dopamine antagonist SCH23390 or the D2 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 D2 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.

Lever-pressing behavior reinforced by intravenous infusion of various concentrations of heroin, and consequent development of physical dependence, were examined in rats. In addition, the influence of opiate dependence, and of its disappearance following withdrawal, on heroin self-administration were investigated. It was found that intravenous self-administration of heroin at 0.03 mg/kg/infusion maintained self-administration behavior without producing physical dependence. Total responses per session decreased with increasing unit dose of heroin, whereas the total amount of drug self-administered was directly related to unit dose. Significantly greater numbers of withdrawal signs and percentage body weight losses in response to naloxone injections were observed following self-administration of heroin at 0.1, 0.3 or 0.6 mg/kg/infusion. Intake of heroin at 0.03 mg/kg/infusion, but not at 0.1, 0.3 or 0.6 mg/kg/infusion, was found to increase significantly in opiate-dependent and postdependent animals. These findings support the previous use of 0.03 mg/kg/infusion as a suitable dose for illustrating the reinforcing effect of heroin without the influence of physical dependence.