Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress.
Neuropharmacology July 1, 2024 Kevin T Krupp, Jazmine D W Yaeger, Leighton J Ledesma et al. 11 citations
A single low dose of the psychedelic compound (R)-DOI, a selective 5-HT2A receptor partial agonist, can shift stress-coping behavior in male mice exposed to repeated social aggression. In the Stress Alternatives Model, mice that typically adopt reactive, vulnerable coping strategies (Stay) showed increased escape behavior, more attention to escape routes, and reduced freezing after treatment. These behavioral changes were accompanied by reduced levels of the inflammatory cytokine TNFα in both plasma and limbic brain regions. Stay animals had heightened cytokine gene expression, and both Stay and Escape mice showed elevated TNFα compared to unstressed controls. The findings suggest that (R)-DOI's anxiolytic effects may be linked to its anti-inflammatory properties.