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 hipp ocampus, and this effect could contribute to the atrophy of hippocampal neu rons. This study examines the influence of selective 5-HT, as well as norep inephrine, receptor antagonists on the stress-induced down-regulation of BD NF mRNA. Pretreatment with a selective 5-HT2A receptor antagonist, MDL100,9 07, significantly blocked the influence of stress on expression of BDNF mRN A. In contrast, pretreatment with either a selective 5-HT2c or 5-HT1A recep tor antagonist did not influence the stress-induced decrease in levels of B DNF mRNA. The stress-induced decrease was also not influenced by pretreatme nt with antagonists of beta(1/2)- or alpha(1)-adrenergic, or CRF-R1 recepto rs, The results demonstrate that 5-HT2A receptors mediate, at least in part , the stress-induced down-regulation of BDNF expression in the rat hippocam pus. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.