5-HT2A Receptors and BDNF Regulation: Implications for Psychopathology

Abstract

Serotonin2A (5-HT2A) receptors are implicated in the pathophysiology of mood disorders and schizophrenia, as well as in mediating the effects of hallucinogens. 5-HT2A receptors also serve as drug targets for specific classes of antidepressants and atypical antipsychotics. Preclinical and clinical studies have identified an important role for brain derived neurotrophic factor (BDNF) in the pathogenesis of depression and schizophrenia, and in the therapeutic actions of antidepressants and antipsychotics. 5-HT2A receptors have been reported to regulate BDNF expression within key limbic neurocircuits, including the prefrontal cortex and hippocampus. Further, alterations in BDNF directly impact 5-HT2A receptor expression, signaling and function. In this book chapter, we have extensively reviewed the current understanding of the regulation of BDNF by 5-HT2A receptors at multiple levels spanning from transcriptional regulation to modulation of BDNF signaling. We have also discussed the impact of perturbations in BDNF on 5-HT2A receptors, primarily focusing on studies from BDNF mouse mutant models. These studies highlight a reciprocal relationship between 5-HT2A receptors and BDNF, and suggest that such a crosstalk may play an important role in the actions of stress, antidepressant and atypical antipsychotic treatments, and in mediating hallucinogenic responses. We also highlight specific open questions hitherto unexplored in understanding the nature of interaction between 5-HT2A receptors and BDNF, and the implications of such a relationship to psychopathology.