Fig. 10.
Cellular models for 5-HT2A receptor regulation of BDNF mRNA in neocortex and hippocampus. Within the neocortex, application of 5-HT/DOI has been shown to induce EPSPs in layer V pyramidal neurons via activation of 5-HT2Areceptors (5-HT2A-R). The increase in EPSPs is a result of increased release of glutamate (GLU) and activation of AMPA receptors (AMPA-R) and can be blocked by the selective AMPA receptor antagonist LY 293558. This suggests that the upregulation of BDNF mRNA by DOI may be mediated via a release of glutamate and an increase in neuronal activity. In contrast, DOI treatment leads to a decrease in levels of BDNF mRNA in the dentate gyrus granule cell layer of the hippocampus. This could be mediated by activation of 5-HT2A receptors located on GABAergic interneurons. Activation of 5-HT2A receptors increases the firing rate of GABAergic interneurons and thereby increases IPSPs in the granule cells. The increased inhibitory control of dentate gyrus granule cells could lead to downregulation of BDNF mRNA.