Subanesthetic Ketamine Ameliorates Activity-Based Anorexia of Adult Mice

Objective: Anorexia nervosa (AN) is an eating disorder with the second highest mortality of all mental illnesses and high relapse rate, especially among adult females, yet with no accepted pharmacotherapy. A small number of studies have reported that adult females who struggled with severe and relapsing AN experienced sustained remission of the illness following ketamine infusions. Two other reports showed that 30 mg/kg IP ketamine can reduce vulnerability of adolescent mice to activity-based anorexia (ABA), an animal model of AN. However, no study has tested the efficacy of ketamine on adult ABA mice. This study aimed to fill this gap in knowledge.

Methods: Forty-one female mice underwent three cycles of ABA (ABA1, ABA2, and ABA3) to assess relapse vulnerability in adulthood. Of them, 13 received ketamine injections (30 mg/kg, 3 doses) during ABA2 (KET) in adulthood to assess ketamine's acute effects during ABA2 and ketamine's potential for sustained efficacy during ABA3, 10-13 days later. The remaining 28 received vehicle or no injections during ABA2 (CON).

Results: Severe weight loss (>20% of baseline) during ABA3 was observed for 89% of CON but only 69% of KET. Overall wheel running per day was significantly less for KET than CON (p < 0.01) throughout ABA2, including hours of food availability, and these reductions were sustained through ABA3. Food consumption was not altered significantly by ketamine.

Discussion: These findings suggest that ketamine may reduce adult females' vulnerability to ABA and may protect women from AN relapse by reducing hyperactivity.