Fibroblast growth factor-2 is selectively modulated in the rat brain by E-5842, a preferential sigma-1 receptor ligand and putative atypical antipsychotic

• Published in: The European journal of neuroscience 2001-03, Vol.13 (5), p.909-915
• Main Authors: Ovalle, Sergio, Zamanillo, Daniel, Andreu, Francesc, Farré, Antoni J., Guitart, Xavier
• Format: Article
• Language: English
• Subjects: Animals; Antipsychotic Agents - pharmacology; Brain - drug effects; Brain - metabolism; Clozapine - pharmacology; Dose-Response Relationship, Drug; Fibroblast Growth Factor 2 - drug effects; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; gene regulation; Male; negative symptoms; neuroleptic; Neurons - drug effects; Neurons - metabolism; polymerase chain reaction; prefrontal cortex; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, sigma - drug effects; Receptors, sigma - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; schizophrenia; Schizophrenia - drug therapy; Schizophrenia - metabolism; Schizophrenia - physiopathology; Sigma-1 Receptor; Triazoles - pharmacology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.0953-816x.2001.01459.x

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.