Serotonergic psychedelics such as psilocybin, the psychoactive substance found in the magic mushroom, have hallucinatory effect through stimulation of the cortical serotonin 5-HT2A receptor (5-HT2A). Recently, FDA has called psilocybin a 'breakthrough therapy' for severe depression. We have already demonstrated that 5-HT2A in the lateral septum (LS) plays a responsible role in...
Recently, FDA approved psilocybin, the psychoactive substance found in the magic mushroom, as a "breakthrough therapy" for depression; however, its detailed mechanism remains unknown. Serotonergic psychedelics such as psilocybin and LSD have hallucinatory effect through stimulation of serotonin 5-HT2A receptor (5-HT2A), motivating us to investigate the role of 5-HT2A stimulation in...
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the prototype for a potential new generation of glutamate-based antidepressants that rapidly relieve symptoms of depression within hours of treatment. Studies in rodents have demonstrated that neuroplasticity in the medial prefrontal cortex (mPFC) is critical for the antidepressant actions of ketamine. However, effector circuits...
The antidepressant actions of the NMDA receptor antagonist ketamine require activity-dependent release of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). Our recent study shows a similar requirement for vascular endothelial growth factor (VEGF). Previous studies have reported that both BDNF and VEGF activate TRPC3 and TRPC6 via diacylglycerol production, and...
Previous studies have shown that activity-dependent release of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) is required for the antidepressant actions of ketamine. Recently, we have found that neuronal vascular endothelial growth factor (VEGF),signaling in the mPFC also plays a crucial role in the antidepressant actions of this rapid acting agent. However, it...
Background: The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine exerts rapid and sustained antidepressant effects in depressed patients. Ketamine is a racemic mixture of equal amounts of enantiomers, (R)-ketamine and (S)-ketamine. The neural mechanisms that underlie different effects of these enantiomers remain unclear.