Sex specific effects of ketamine, but not other glutamate receptor modulators, on ethanol self-administration and reinstatement of ethanol seeking in rats.
Psychopharmacology April 8, 2025 Megan L Bertholomey, Camryn Forbes, Bryan D McElroy et al. 3 citations
Ketamine reduces alcohol seeking in female but not male rats, including in a model of stress combined with cues that trigger relapse. A dose of 10 mg/kg ketamine selectively lowered alcohol self-administration and stress-plus-cue-induced reinstatement of alcohol seeking in females. The same dose reduced reinstatement of saccharin seeking in both sexes. The NMDA receptor antagonist memantine reduced alcohol seeking in both sexes, while the ketamine metabolite hydroxynorketamine had no effect. These findings suggest that NMDA receptor antagonism may broadly reduce stress-related alcohol seeking, but ketamine has unique properties producing female-specific effects on alcohol-motivated behaviors.