Interactions between environmental stimulation and antipsychotic drug effects on forebrain C-FOS activation

The immediate-early gene product Fos is differentially induced in the rat b rain by the antipsychotic drugs haloperidol and clozapine. It is often clai med that although both drugs induce Fos in the nucleus accumbens, haloperid ol but not clozapine increases Fos-like immunoreactivity in the striatum, w hereas clozapine but nor haloperidol increases Fos-like immunoreactivity in prefrontal cortex. Investigations of antipsychotic drug effects on Fos hav e typically administered high doses with pronounced sedative effects to beh aviorally naive animals. In the present study, we compared the effects of l ow doses of haloperidol (0.1 mg/kg) and clozapine (5 mg/kg) on Fos-like imm unoreactivity in rats which were either behaviorally naive, exposed to a no vel environment or tested for two-way active avoidance. We determined that haloperidol increased Fos in the striatum and nucleus accumbens regardless of testing condition whereas clozapine markedly reduced the induction of Fo s by behavioral testing in these regions: moreover, haloperidol dramaticall y increased prefrontal cortical Fos expression in animals placed in a novel environment, bur not in testing-naive controls. From these results we sugg est that antipsychotic drug-induced patterns of Fos expression in the rat a re highly dependent on animals' concurrent behavioral status. perhaps refle cting neuroanatomically specific interactions between antipsychotic drugs a nd environmental stressors which also may occur in the schizophrenic condit ion. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.