ACUTE ADMINISTRATION OF TYPICAL AND ATYPICAL ANTIPSYCHOTIC-DRUGS INDUCES DISTINCTIVE PATTERNS OF FOS EXPRESSION IN THE RAT FOREBRAIN

Fos expression in the rat brain was investigated by immunohistochemist ry after i.p. administration of single doses of a wide range of typica l neuroleptic antipsychotic drugs (including the potent dopamine D2 an tagonist haloperidol and the mixed monoamine antagonist chlorpromazine ) and atypical antipsychotic drugs (including the weak dopamine D2 ant agonists clozapine and thioridazine, the relatively pure D2 antagonist raclopride and the mixed D2 and serotonin S2 antagonist risperidone). For comparison to the effects of the antipsychotic drugs and also bec ause the unique clinical therapeutic effects of clozapine have been at tributed to S2 blockade, the S2 antagonist ritanserin was also studied . The single shared effect of all antipsychotic drugs tested was the i nduction of significantly increased Fos immunoreactivity in the nucleu s accumbens (NAc). Fos-positive neurons in the NAc were mostly localiz ed in patches throughout its rostrocaudal extent. Haloperidol, chlorpr omazine, raclopride and risperidone all significantly increased Fos ex pression in the medial and lateral striatum. Fos-positive neurons in t he striatum were distributed more lateral than medial and declined fro m rostral to caudal levels. Haloperidol, thioridazine and risperidone also markedly increased Fos expression in the lateral septum. Distingu ishing it from the other neuroleptics, clozapine did not increase Fos expression in the lateral striatum, but induced a significant increase in Fos expression in the prefrontal cortex. Ritanserin did not induce Fos expression in any brain region examined, suggesting that S2 antag onism is not responsible for the effects of antipsychotic drugs observ ed here. Our results suggest that there are distinctive patterns of Fo s expression in the forebrain induced by typical and atypical antipsyc hotic drugs. Notably, Fos expression in the NAc, as a shared property of all the antipsychotic drugs, may be related to the actions mediatin g the therapeutic effects of these drugs in the treatment of psychotic disorders. The density of Fos-positive neurons stimulated by antipsyc hotic drugs in the striatum appeared to be correlated with the relativ e severity of extrapyramidal side-effects produced by these drugs and may be related to the mechanisms mediating these effects.