5-HT_2A: Its role in frontally mediated executive function and related psychopathology

Serotonin (5-HT)_2A receptors are widely distributed, with high levels in the frontal cortex, where postsynaptic activation may increase activity in pyramidal glutamatergic neurons and mediate various executive functions. More specifically, reciprocal cortical-raphe pathways may allow the ventral prefrontal cortex to inhibit stress-induced neural activity in the brainstem when stressors are perceived as controllable. However, early adversity and negative attitudes may be associated with higher frontal 5-HT_2A receptor levels and greater risk for stress-induced psychopathology, and certain 5-HT_2A gene variants have been associated with increased risk for impulsive behavior. Conversely, many antidepressants result in decreased levels of 5-HT_2A receptor levels, and blockade of 5-HT_2A receptors has proven useful in the treatment of a number of psychiatric disorders.