LSD Restores Synaptic Plasticity in VTA of Morphine-Treated Mice and Disrupts Morphine-Conditioned Place Preference.
bioRxiv : the preprint server for biology June 15, 2025 Michael Von Gunten, Tenna Russell, Isaac Stirland et al. preprint
A single high dose or four microdoses of LSD accelerated the extinction of morphine-induced conditioned place preference in both male and female mice. Whole-cell electrophysiology showed that excitatory synaptic plasticity in VTA GABA neurons, which was suppressed after morphine exposure, was restored 24 hours after a single high dose of LSD. Whole-brain DNA methylation analysis revealed significant differences in methylation profiles between morphine-treated mice that received LSD versus saline. These findings suggest that LSD may reverse or prevent morphine-induced changes in reward circuit plasticity and reduce measures of morphine preference.