Agonist-Directed Signaling of Serotonin 5-HT2C Receptors Differences Between Serotonin and Lysergic Acid Diethylamide (LSD)

Lysergic acid diethylamide (LSD) modifies serotonin neurotransmission, and new molecular techniques reveal that its signaling at serotonin 5-HT2C receptors differs from that of the endogenous agonist serotonin. RNA editing of the 5-HT2C receptor dramatically alters LSD's ability to stimulate phosphatidylinositol signaling, offering insight into the mechanisms of partial agonism.

Study at a glance

Abstract

For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist serotonin. In addition, RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate phosphatidylinositol signaling. These findings provide a unique opportunity to understand the mechanism(s) of partial agonism.