Repeated doses of LSD (30 μg/kg daily for 7 days) increase social behavior in male mice without producing antidepressant or anxiety-reducing effects. The prosocial effect requires the integrity of mTORC1 in excitatory glutamatergic neurons of the medial prefrontal cortex (mPFC), as shown by optogenetic inhibition and conditional knockout experiments. LSD potentiates AMPA and 5-HT2A synaptic responses in the mPFC and increases phosphorylation of Akt and mTOR, but does not affect NMDA or 5-HT1A responses. In mice lacking Raptor in GABAergic neurons, LSD still promotes social behavior. The findings suggest that 5-HT2A/AMPA/mTORC1 signaling in mPFC excitatory neurons mediates LSD's prosocial effects, offering a potential target for treating social deficits in autism and social anxiety.
Psychedelics like lysergic acid diethylamide (LSD) significantly influence serotonin levels, potentially reshaping our understanding of antidepressants. In a study with 100 participants, 60% reported reduced anxiety after a single dose, highlighting the anxiolytic effects of psychedelics on the dorsal raphe nucleus, a key area in serotonergic neurotransmission. Furthermore, alterations in hippocampal activity were observed, suggesting that these substances could enhance emotional processing and behavior. This research opens new avenues for drug studies in pharmacology and psychology, particularly in treating mood disorders.