Serotonin (5-hydroxytryptamine, 5-HT) neurons originate in the raphe nuclei of the pons and cerebellum and project widely to subcortical and cortical structures, including both medial and orbital aspects of the prefrontal cortex. The 5-HT2A receptor subtype is thought to mediate many of the effects of psychedelic hallucinogens such as lysergic acid diethylamide, and dysregulation of 5-HT signaling in PFC is thought to contribute to the pathology of schizophrenia and mood disorders. Although 5-HT activates a large number of receptors including an ion channel subtype (5-HT3), 5-HT1A and 5-HT2A receptors are thought to be the predominant forms expressed by PFC neurons (Kia et al., 1996; Willins et al., 1997; Santana et al., 2004). Activation of 5-HT2A receptors enhances the frequency of both inhibitory and excitatory postsynaptic currents recorded in pyramidal neurons, with less effect noted for interneurons (Zhou and Hablitz, 1999). The 5-HT2A-dependent increase in spontaneous events was not observed in the presence of TTX suggesting that these receptors do not alter presynaptic release of glutamate. Whereas 5-HT or 5-HT2A agonists generate only small, subthreshold depolarizations in most PFC pyramidal neurons
