Selective modulation of fibroblast growth factor-2 expression in the rat brain by the atypical antipsychotic clozapine

In the present paper we investigated, in the rat brain, the expression of b asic fibroblast growth factor (FGF-2) in response to the atypical antipsych otic clozapine. We found that acute or chronic administration of this compo und produced a selective increase of FGF-2 mRNA and protein in the striatum . Although acute injection of clozapine did increase FGF-2 expression in pa rietal cortex and nucleus accumbens we found that, following repeated admin istration, the induction of the trophic molecule was taking place only at s triatal level. The analysis of other antipsychotic drugs did not provide co nclusive evidence for the molecular mechanisms involved in clozapine-induce d elevation of FGF-2. In fact, chronic administration of classical neurolep tics, haloperidol and chlorpromazine, did not alter the expression of FGF-2 . Furthermore the novel drugs quetiapine and olanzapine, despite some simil arities in their receptor profiles, were similarly ineffective. Hence these data suggest that, among antipsychotic drugs, the induction of FGF-2 is un ique to clozapine. On the basis of the neuroprotective activity of this tro phic molecule, our data might be relevant for the potential use of clozapin e in tardive dyskinesia and parkinsonism, which develop during long term ad ministration of classical neuroleptic drugs. (C) 1999 Elsevier Science Ltd. All rights reserved.