title: Mecamylamine attenuates dexamethasone-induced anxiety-like behavior in association with brain derived neurotrophic factor upregulation in rat brains.
abstract: Mecamylamine (MEC), which was initially developed as a ganglionic blocker for the treatment of hypertension has been investigated as a potent antagonist for most types of nicotinic acetylcholine receptors (nAChRs). Most studies of MEC have focused on its inhibitory effects for nAChRs; however its biological uses have recently been expanded to the treatment of psychological disorders accompanying anxiety-related symptoms. Although MEC shows obvious anxiolytic action, there is no clear evidence on its function. In this study, we investigated whether MEC affects brain derived neurotrophic factor (BDNF) expression in vitro and in vivo. MEC increased BDNF expression in differentiated SH-SY5Y cells and the cerebral cortex region of rat brains. To determine if the anxiolytic effect of MEC is associated with BDNF upregulation, the elevated plus maze (EPM) task was conducted in a dexamethasone (DEX)-induced anxiety model. MEC reduced DEX-induced anxiety-like behavior, and increased BDNF expression in the cerebral cortex of rats. These results suggest that the anxiolytic effect of MEC in EPM might be associated with BDNF upregulation in the cerebral cortex region of rats. The therapeutic efficacy of MEC for anxiety might be partly dependent on BDNF modulation.
authors.affiliation: Biochemistry Laboratory, Department of Biological Science, Sungkyunkwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, South Korea.
authors.forename: Dong Ik
authors.initials: DI
authors.lastname: Park
authors.forename: Hong Gi
authors.initials: HG
authors.lastname: Kim
authors.forename: Woo Ram
authors.initials: WR
authors.lastname: Jung
authors.forename: Min Kyoo
authors.initials: MK
authors.lastname: Shin
authors.forename: Kil Lyong
authors.initials: KL
authors.lastname: Kim
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014151:Anti-Anxiety Agents; D019208:Brain-Derived Neurotrophic Factor; D008464:Mecamylamine; D003907:Dexamethasone