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 D-2 and 5-hydroxytryptamine(2) (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 ford-amphetamine was linked to the dose of drug received. The mixed D-2 and 5-HT2, receptor antagonist risperidone (0.1, 0.2, and 0.4 mg/kg) reduced responding for d-amphetamine (60 mu g/kg infusion). The selective D-2 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 after 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. (C) 1998 Elsevier Science Inc.