EFFECTS OF D-2 DOPAMINE-RECEPTOR ANTAGONISTS ON FOS PROTEIN EXPRESSION IN THE STRIATAL COMPLEX AND ENTORHINAL CORTEX OF THE NONHUMAN PRIMATE

Recent studies have reported that acute administration of dopamine D-2 receptor antagonists increases expression of the immediate early gene c-fos in the rat striatal complex. There have been no corresponding s tudies of the effects of D-2 antagonists in primate species. Since all clinically effective antipsychotic drugs share D-2 receptor antagonis m, it is important to define the extent to which these drugs may alter expression of c-fos or its protein product, Fos, in primates. We ther efore examined the effects of administration of two D-2 receptor antag onists, haloperidol and metoclopramide, on Fos expression in the stria tum and temporal cortices of the vervet monkey. Metoclopramide does no t appear to possess significant antipsychotic efficacy but potently pr oduces extrapyramidal side effects, while haloperidol is an effective antipsychotic drug that produces extrapyramidal side effects. Both dru gs increased the number of Fos-like immunoreactive (Fos-li) neurons in the caudate nucleus and putamen; the numbers of Fos-li neurons in the se regions were increased in both the patch and matrix compartments. H aloperidol but not metoclopramide increased the number of Fos-li neuro ns in the nucleus accumbens shell. Similarly, haloperidol but not meto clopramide increased the number of Fos-li neurons in the entorhinal co rtex. Neither drug altered Fos expression in the inferior temporal cor tex. These data suggest that the dorsolateral caudate nucleus and puta men may be sites at which D-2 receptor antagonists elicit extrapyramid al side effects, and the nucleus accumbens shell and entorhinal cortex may be loci at which the therapeutic actions of antipsychotic drugs a re manifested. (C) 1996 Wiley-Liss, Inc.