MIXED D-2 5-HT2A ANTAGONISM OF COCAINE-INDUCED FACILITATION OF BRAIN-STIMULATION REWARD/

Previous behavioral, neurochemical and neurophysiological experiments have shown that selective 5-HT2A and mixed D-2/5-HT2A antagonists can attenuate some, but not all, responses to amphetamine. The generality of these findings were determined in the present experiment by assessi ng the effect of mixed D-2/5-HT2A antagonists on cocaine-induced facil itation of ventral tegmental area self-stimulation in rats. Although a mphetamine and cocaine influence activity in monoaminergic neurons thr ough different mechanisms, our previous research has shown that select ive D-2 and 5-HT2A antagonists have similar effects on behavioral resp onses to these psychostimulants. Therefore, we expected a similar patt ern of results using mixed D-2/5-HT2A antagonists, As shown previously , cocaine decreased self-stimulation threshold in a dose-dependent man ner. Haloperidol and the mixed D-2/5-HT2A antagonists risperidone and MDL 28, 133A antagonized cocaine-induced facilitation of self-stimulat ion, but only at doses that increased baseline self-stimulation thresh old. There was a significant correlation (r = 0.87, p < 0.001) between antagonist-induced change in baseline threshold and attenuation of co caine's effect on threshold, Taken together, the results of this and p revious experiments support the importance of D-2 receptors in the mec hanisms of brain stimulation reward. 5-HT2A receptors appear not to be involved in mediation of both brain stimulation reward and amphetamin e-and cocaine induced facilitation of brain stimulation reward. (C) 19 98 Elsevier Science Inc.