Role of 5-HT2A receptors in the stress-induced down-regulation of brain-derived neurotrophic factor expression in rat hippocampus

Immobilization stress decreases the expression of BDNF mRNA in the rat hippocampus, and this effect could contribute to the atrophy of hippocampal neurons. This study examines the influence of selective 5-HT, as well as norepinephrine, receptor antagonists on the stress-induced down-regulation of BDNF mRNA. Pretreatment with a selective 5-HT2A receptor antagonist, MDL100,907, significantly blocked the influence of stress on expression of BDNF mRNA. In contrast, pretreatment with either a selective 5-HT2c or 5-HT1A receptor antagonist did not influence the stress-induced decrease in levels of BDNF mRNA. The stress-induced decrease was also not influenced by pretreatment with antagonists of beta(1/2)- or alpha(1)-adrenergic, or CRF-R1 receptors, The results demonstrate that 5-HT2A receptors mediate, at least in part, the stress-induced down-regulation of BDNF expression in the rat hippocampus. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.