S-ketamine, but not R-ketamine, transiently suppresses front-loaded binge-like alcohol self-administration in male rats
July 12, 2026 Fahd François Hilal, Méléna Dreinaza, Quentin Lebel et al.
S-ketamine, but not R-ketamine, dose-dependently suppresses binge-like alcohol self-administration in male rats, with the strongest effect at 40 mg/kg. This suppression is selective, occurring without sedation or motor impairment, and is most pronounced on front-loaded drinking. However, the effect rapidly diminishes with repeated doses, indicating rapid tolerance. R-ketamine does not alter alcohol intake under the same conditions, nor does prior R-ketamine exposure affect subsequent S-ketamine efficacy. The findings suggest that stereochemistry, dosing schedule, and alcohol exposure pattern are key determinants of ketamine's potential for treating alcohol use disorder.