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.
In a rat model of schizophrenia created by perinatal phencyclidine (PCP) exposure, antipsychotic treatment with haloperidol or clozapine reduced altered glucocorticoid receptor (GR) sensitivity in the brain. The study measured corticosterone levels and GR-related proteins (GR, pGR, HSP70, HSP90, FKBP51, and 11β-HSD) in different brain regions of adult male rats. Six groups were treated with PCP or saline on postnatal days 2, 6, 9, and 12; some groups then received haloperidol or clozapine from day 35 to 100. The findings indicate disturbances in the HPA axis in this schizophrenia model and suggest antipsychotics may have protective effects against such dysregulation.