Established sensitization of ethanol-induced locomotor activity is not reversed by psilocybin or the 5-HT2A receptor agonist TCB-2 in male DBA/2J mice.
Pharmacology, biochemistry, and behavior February 1, 2024 Paul J Fletcher, Zhaoxia Li, Xiao Dong Ji et al. 2 citations
Psychedelic drugs that activate the 5-HT2A receptor, such as psilocybin, show promise for treating alcohol-use disorders. This study tested whether psilocybin or the 5-HT2A agonist TCB-2 could reverse the sensitized locomotor activity caused by repeated ethanol exposure in male DBA/2J mice. Mice received repeated ethanol injections to induce sensitization, then five daily doses of psilocybin (0, 0.3, or 1 mg/kg) or TCB-2 (0, 1, or 3 mg/kg). A subsequent ethanol challenge showed that sensitized mice still had enhanced activity, and neither psilocybin nor TCB-2 reduced this sensitized response. The results suggest that these drugs' short-term effects on ethanol intake may not involve reversing long-term behavioral or neural adaptations from repeated ethanol exposure.