Lysergic acid diethylamide (LSD) enhances social behavior in mice by increasing excitatory neurotransmission in the medial prefrontal cortex, specifically through activation of 5-HT2A and AMPA receptors and the mTORC1 protein complex, a study finds. LSD is a psychedelic drug that increases empathy, trust, altruism, and feelings of connectedness to others. The neurobiological mechanisms underlying the drug's prosocial effects are unclear. To uncover the underlying mechanism, Nahum Sonenberg, Gabriella Gobbi, and colleagues used a combination of electrophysiology, optogenetics, behavioral paradigms, and molecular biology techniques in mice. LSD treatment increased the amount of time mice spent interacting with an unfamiliar mouse, compared with treatment with the control. The social effects of LSD were eliminated when the medial prefrontal cortex was pretreated with infusions of drugs that block 5-HT2A and AMPA receptors. Similarly, the social effects of LSD were blocked by optogenetic silencing of excitatory neurons in the medial prefrontal cortex. In mice that were genetically engineered to lack the intact mTORC1 protein complex in excitatory neurons in the prefrontal cortex, LSD-induced signaling through 5-HT2A and AMPA receptors was altered, and LSD did not enhance sociability. According to the authors, the findings could inform the development of therapies for autism spectrum disorder and social anxiety disorder.
Article #20-20705: "Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission," by Danilo De Gregorio et al.
Proceedings of the National Academy of Sciences