A comparison of the effects of risperidone, raclopride, and ritanserin on intravenous self-administration of d-amphetamine.

These experiments were conducted to examine the effects of simultaneous blockade of dopamine D2 and 5-hydroxytryptamine2 (5-HT) receptor function on responding for intravenous infusions of d-amphetamine. Rats were trained to self-administer d-amphetamine intravenously according to a progressive ratio schedule of reinforcement, in which response requirements increased for successive infusions until responding extinguished. In the first experiment it was shown that increases in the unit infusion dose of d-amphetamine resulted in an increase in the number of amphetamine infusions earned. Thus, the strength of responding for d-amphetamine was linked to the dose of drug received. The mixed D2 and 5-HT2 receptor antagonist risperidone (0.1, 0.2, and 0.4 mg/kg) reduced responding for d-amphetamine (60 microg/kg infusion). The selective D2 antagonist raclopride (0.1, 0.2, and 0.4 mg/kg) also reduced responding for d-amphetamine. In contrast, the selective 5-HT2 antagonist ritanserin (0.63, 1.25, and 2.5 mg/kg) failed to alter amphetamine self-administration. Combined injections of raclopride (0.05 or 0.1 mg/kg) and ritanserin (2.5 mg/kg) were no more effective than injections of raclopride alone in reducing responding for d-amphetamine. Overall, these results suggest that 5-HT2 receptor blockade plays a negligible role in the rewarding effects of d-amphetamine measured by intravenous self-administration, and does not contribute to the suppressant effects of risperidone on this behavior.