5-HT2A RECEPTOR-MEDIATED REGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR MESSENGER-RNA IN THE HIPPOCAMPUS AND THE NEOCORTEX

The influence of 5-HT receptor agonists on the expression of BDNF in b rain was determined. Administration of a hallucinogenic 5-H-2A/2C rece ptor agonist, but not a 5-HT1A receptor agonist, resulted in a signifi cant but differential regulation of BDNF mRNA levels in hippocampus an d neocortex. In the hippocampus, the 5-HT2A/2C receptor agonist signif icantly decreased BDNF mRNA expression in the dentate gyrus granule ce ll layer but did not influence expression of the neurotrophin in the C A subfields. In parietal cortex and other neocortical areas, but not p iriform cortex, the 5-HT2A/2C receptor agonist dramatically increased the expression of BDNF mRNA. The effect of the 5-HT2A/2C receptor agon ist on BDNF mRNA in both the hippocampus and the neocortex was blocked by pretreatment with a selective 5-HT2A, but not 5-HT2C, receptor ant agonist. The expression of BDNF mRNA in the hippocampus is reported to be decreased by stress, raising the possibility that the 5-HT2A recep tor mediates this effect. Pretreatment with ketanserin, a 5-HT2A/2C re ceptor antagonist, significantly blocked the stress-induced downregula tion of BDNF mRNA in hippocampus, in support of this hypothesis. The r esults of this study raise the possibility that regulation of BDNF exp ression by hallucinogenic 5-HT2A receptor agonists leads to adaptation s of synaptic strength in the hippocampus and the neocortex that may m ediate some of the acute and long-term behavioral effects of these age nts.