Ma. Riva et al., Selective modulation of fibroblast growth factor-2 expression in the rat brain by the atypical antipsychotic clozapine, NEUROPHARM, 38(7), 1999, pp. 1075-1082
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.
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