Methamphetamine-Fentanyl Polysubstance Administration Produces Social Deficits and Corticolimbic Stress-Reward Circuit Adaptations.
Research square April 23, 2026 Leah M Salinsky, Joshua L Fox, Kyra C Diaz et al.
Withdrawal from repeated use of methamphetamine and fentanyl together reduces social preference in rats, confirming earlier findings that polysubstance withdrawal impairs social behavior. A single dose of psilocybin did not restore sociability within 24 hours. In the medial prefrontal cortex, psilocybin had opposite effects on CRHR1 gene expression depending on drug history: it decreased expression in control rats but increased it in polysubstance-treated rats. In the nucleus accumbens, polysubstance treatment reduced CRHR1 expression. OPRM1 expression was sex-dependent, with a marked reduction in the nucleus accumbens of females after polysubstance treatment and sex-dependent effects in the medial prefrontal cortex.