LIMBIC-PREFRONTAL CONNECTIVITY AND CLOZAPINE

The mechanisms of the antipsychotic efficacy and side effect profile o f clozapine are incompletely understood. In vivo pharmacologic studies suggest that while clozapine does produce D2 receptor blockade, its u nusual clinical profile may relate to activity at other receptor sites and to anatomical areas outside the striatum. Rodent studies indicate that acute administration of clinical doses of antipsychotic drugs, i ncluding clozapine, induces Fos (the protein product of the immediate early gene, c-fos) in the nucleus accumbens. However, unlike typical a ntipsychotic drugs, clozapine does not induce Fos in the dorsal striat um and does induce Fos in medical portions of the prefrontal cortex. C lozapine seems to produce a unique signature effect on long-term neuro nal metabolism in its induction of Fos in the shell of the nucleus acc umbens and in the medical prefrontal cortex. Future in vivo studies of cerebral blood flow and glucose metabolism in human patients may help to elucidate the specificity and reproducibility of the effects of cl ozapine in the ventral striatum and prefrontal cortex.