Clozapine- and olanzapine-induced Fos expression in the rat medial prefrontal cortex is mediated by β-adrenoceptors

The atypical neuroleptics, clozapine and olanzapine, have superior therapeutic efficacy against thr negative symptoms of schizophrenia, compared with the typical neuroleptics. Recently, it has been suggested that the ability of clozapine and olanzapine to induce Fos expression in the medial prefrontal cortex (mPFC), contribute to their therapeutic efficacy. However, the mechanisms underlying the neuropharmacological effects of clozapine and olanzapine in the mPFC remain elusive. In the present study, we demonstrate that clozapine- and olanzapine-induced Fos expression in the mPFC are inhibited by propranolol. We also show that clozapine and olanzapine induce Fos expression in the locus coeruleus. These results suggest that clozapine and olanzapine increase noradrenaline releases by stimulating noradrenergic neuronal activity in the locus coeruleus and, consequently, increased noradrenaline induce Fos expression in the Fos expression in the mPFC via beta-adrenergic receptors. This postulated sequence may be one of mechanisms by which clozapine-like atypical neuroleptics are more effective for the negative symptoms of schizophrenia. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.