Ketamine-induced static and dynamic functional connectivity changes are modulated by opioid receptors and biological sex in rats.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology April 19, 2025 Valeria Grasso, Joseph Tennyson, Raag D Airan et al. 5 citations
Ketamine, a rapid-acting treatment for depression and other neuropsychiatric disorders, works partly through the brain's opioid system, and its effects differ by sex. In rats given ketamine, blocking opioid receptors with naltrexone altered functional connectivity changes in the brain, especially in the medial prefrontal cortex (mPFC), a region of the default-mode network. These connectivity changes depended on biological sex: naltrexone affected mPFC connectivity patterns differently in males and females. Ketamine also caused a shift toward greater brain dysconnectivity and entropy, but only in male rats and only when opioid receptors were available. The findings suggest sex-specific interactions between ketamine and opioid receptors that warrant further study.