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 basic fibroblast growth factor (FGF-2) in response to the atypical antipsychotic clozapine. We found that acute or chronic administration of this compound produced a selective increase of FGF-2 mRNA and protein in the striatum. Although acute injection of clozapine did increase FGF-2 expression in parietal cortex and nucleus accumbens we found that, following repeated administration, the induction of the trophic molecule was taking place only at striatal level. The analysis of other antipsychotic drugs did not provide conclusive evidence for the molecular mechanisms involved in clozapine-induced elevation of FGF-2. In fact, chronic administration of classical neuroleptics, haloperidol and chlorpromazine, did not alter the expression of FGF-2. Furthermore the novel drugs quetiapine and olanzapine, despite some similarities in their receptor profiles, were similarly ineffective. Hence these data suggest that, among antipsychotic drugs, the induction of FGF-2 is unique to clozapine. On the basis of the neuroprotective activity of this trophic molecule, our data might be relevant for the potential use of clozapine in tardive dyskinesia and parkinsonism, which develop during long term administration of classical neuroleptic drugs.
Riva
M A
MA
Center for Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Italy. mariva@imiucca.csi.unimi.it
Molteni
R
R
Tascedda
F
F
Massironi
A
A
Racagni
G
G
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D014150:Antipsychotic Agents; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D003024:Clozapine