Role of the Serotonin 5-HT_2A Receptor in Learning

Abstract

This study reviews the role of the serotonin 5-HT_2A receptor in learning as measured by the acquisition of the rabbit's classically conditioning nictitating membrane response, a component of the eyeblink response. Agonists at the 5-HT_2A receptor including LSD (d-lysergic acid diethylamide) enhanced associative learning at doses that produce cognitive effects in humans. Some antagonists such as BOL (d-bromolysergic acid diethylamide), LY53,857, and ketanserin acted as neutral antagonists in that they had no effect on learning, whereas others (MDL11,939, ritanserin, and mianserin) acted as inverse agonists in that they retarded learning through an action at the 5-HT_2A receptor. These results were placed in the context of what is known concerning the anatomical distribution and electrophysiological effects of 5-HT_2A receptor activation in frontal cortex and hippocampus, as well as the role of cortical 5-HT_2A receptors in schizophrenia. It was concluded that the 5-HT_2A receptor demonstrates constitutive activity, and that variations in this activity can produce profound alterations in cognitive states.