Effect of the novel sigma1 receptor ligand and putative atypical antipsychotic E-5842 on BDNF mRNA expression in the rat brain.
Changes in the expression of brain-derived neurotrophic factor (BDNF) have been implicated in some neuropsychiatric disorders. Several antipsychotic drugs affect the expression of BDNF mRNA in different areas of the rat brain. We examined the effect of single or repeated administration of 4-[4-fluorophenyl]-1,2,3,6-tetra-hydo-1-[4-[1,-2,4-triazol-1-il]butyl]pyridine citrate) (E-5842), a sigma1 receptor ligand and putative atypical antipsychotic drug on the expression of BDNF mRNA in rats. Acute treatment with E-5842 induced a down-regulation of BDNF mRNA levels in the frontal cortex and hippocampus, while a chronic treatment had no effect. Levels of another neurotrophin, nerve growth factor (NGF), remained unaltered after either acute or chronic treatment. The effects suggest that any therapeutic properties of E-5842 are not mediated by stimulation of BDNF or NGF, whereas the regulation of these trophic factors may be part of the mechanism of action of sigma1 receptor ligands.
Ovalle
Sergio
S
Department of Neuropharmacology, Research Center, Esteve, S.A., Verge de Montserrat 221, 08041-Barcelona, Spain.
Andreu
Francesc
F
Pérez
M Pilar
MP
Zamanillo
Daniel
D
Guitart
Xavier
X
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics; D019965:Neurocognitive Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; 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; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology*; D000097605:Sigma-1 Receptor
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D020932:Nerve Growth Factor; D011725:Pyridines; D012333:RNA, Messenger; D017480:Receptors, sigma; D014230:Triazoles; D000097605:Sigma-1 Receptor; C117757:E 5842