Single injection of ketamine during mid‐adolescence promotes long‐lasting resilience to activity‐based anorexia of female mice by increasing food intake and attenuating hyperactivity as well as anxiety‐like behavior

Objective This study tested the effects of ketamine on vulnerability of female adolescent mice to activity‐based anorexia (ABA). Method Twenty‐four female C57Bl/6 J mice underwent ABA induction, which involved exposing wheel‐acclimated adolescent mice to two bouts of food restriction (FR)—the first ABA (P41–44, mid‐adolescence) and the second ABA (P55–59, late adolescence), with recovery in between. Ketamine (3 or 30 mg/kg) or vehicle was given once, on the second day of FR of the first ABA (P42). Food consumption, body weight and wheel running activity were measured daily. Anxiety‐like behaviors were accessed by elevated plus maze on P49 and P62, after weight restoration during the recovery phase. Results Ketamine (30 mg/kg) increased food intake during the first ABA (+38%, p = .015) and facilitated weight gain during recovery (+42%, p = .003). During the second ABA, the effect was manifested as increased food intake (+38%, p = .001) and weight gain (+47%, p = .001) while attenuating FR‐induced wheel running activity (−24%, p = .09) and weight loss (−17%, p = .056). Ketamine also reduced anxiety‐like behaviors. Discussion Thus, single injection of ketamine during mid‐adolescence effectively attenuates vulnerability of female mice to repeated ABA exposures.