Fibroblast growth factor-2 is selectively modulated in the rat brain by E-5842, a preferential sigma-1 receptor ligand and putative atypical antipsychotic.
Fibroblast growth factor-2 (FGF-2) is a member of a large family of trophic factors whose expression is regulated under several conditions in different areas of the brain. The goal of our experiments was to determine whether the administration of 4-(4-fluorophenyl)-1,2,3,6-tetrahydro-1-[4-(1,2,4-triazol-1-il)butyl] pyridine citrate (E-5842), a sigma-1 receptor ligand and putative atypical antipsychotic, could regulate the expression of FGF-2. After chronic treatment with E-5842 (21 days, and the animals killed 24 h after the last administration), an up-regulation was observed of the expression of FGF-2 mRNA in the prefrontal cortex and the striatum, and a down-regulation of the expression of FGF-2 mRNA in the hypothalamus of the rat brain. Acute treatment with E-5842 (one single administration and animals killed 6 h later) up-regulated FGF-2 expression in the prefrontal cortex, the striatum, the hypothalamus and the hippocampus in a dose-dependent manner. The acute up-regulation was transient and disappeared 24 h after E-5842 administration. The induction of FGF-2 in the striatum after repeated administration has been described for clozapine, but our data concerning regulation in the prefrontal cortex suggest that this effect is unique to E-5852 among other antipsychotics. Given the neuroprotective activity of FGF-2, the data presented here might be relevant to the deficit in cognition and other symptoms that appear in schizophrenia.
Ovalle
S
S
Department of Neuropharmacology, Research Center, Laboratoris Esteve, S.A., Verge de Montserrat, 221, 08041-Barcelona, Spain.
Zamanillo
D
D
Andreu
F
F
Farré
A J
AJ
Guitart
X
X
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014230:Triazoles / Q000494:pharmacology*; D000097605:Sigma-1 Receptor
D014150:Antipsychotic Agents; D003024:Clozapine; D016222:Fibroblast Growth Factor 2; D011725:Pyridines; D012333:RNA, Messenger; D017480:Receptors, sigma; D014230:Triazoles; D000097605:Sigma-1 Receptor; C117757:E 5842