Molecular and Cellular Mechanisms for the Polarized Sorting of Serotonin Receptors: Relevance for Genesis and Treatment of Psychosis

The 5-HT2A serotonin receptor represents the principal molecular target for the actions of both classic hallucinogens, which function as agonists, and atypical antipsychotic drugs, which function as inverse agonists. Pharmacological agents that modify the activity of 5-HT2A receptors are known to modulate human perception and cognition. 5-HT2A receptors are found predominantly in the apical dendritic segment and dendritic spines of cortical pyramidal neurons. This review discusses our current understanding of the molecular and cellular mechanisms governing the preferential targeting of 5-HT2A receptors to apical dendrites and dendritic spines. Uncovering the processes responsible for the polarization of 5-HT2A receptors to neuronal subdomains will likely provide crucial insights into the modulating mechanisms that can affect human cognition and perception.