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.

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This study tested the effects of ketamine on vulnerability of female adolescent mice to activity-based anorexia (ABA). 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. 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. Thus, single injection of ketamine during mid-adolescence effectively attenuates vulnerability of female mice to repeated ABA exposures.