THE JOURNALOF PHARMACOLOGYANDEXPERIMENTALTHERAPEUTICS Copyright0 1990by The American Society for Pharmacologyand Experiments.!Therapeutics 5-HT2ReceptorBlockadeby ICI 169,369andother5-HT2

The effects of D-2 dopamine (DA) receptor blockade were mod ulated by ICI 169,369, a selective 5-hydroxytryptamine (5-HTh receptor antagonist, and by other 5-HT2antagonists. Specifically, it appears that blockade of 5-HT2 receptors can attenuate the effects of D-2 receptor blockade on rat stnatal dopaminergic transmission. Thus, the blockade of D-2 receptors by halopendol results in a compensatory increase in rat stnatal DA metabolism, which is enhanced by lCl 169,369. By itself, ICI 169,369 did not significantly alter DA metabolism. Conversely, several corn pounds which possess appreciable activity at 5-HT2 sites in ex vivo binding assays, but possess little activity at D-2 sites (i.e., pirenperone, setoperone, fluperlapine and clozapine), all pro duced large increases in striatal DA metabolism. Therefore, these data suggest that the 5-HT2 component of these compounds