51. Three daily intraperitoneal injections of sub-anesthetic ketamine ameliorate activity-based anor

Objective: To identify ketamine's dosing schedule that ameliorates voluntary food restriction, hyperactivity and body weight loss of adult mice undergoing activitybased anorexia (ABA), an animal model of anorexia nervosa.

Method: Female and male C57BL6 mice underwent three cycles of ABA, starting from mid-adolescence. ABA vulnerability was compared within and across two groups of animals: those injected intraperitoneally with 30 mg/kg ketamine for three consecutive days (30mgKetx3) during the second ABA in late adolescence (ABA2) or with vehicle only (Vx3).

Results: Vx3 females and males exhibited individual differences in wheel running and weight retention during first ABA in mid-adolescence (ABA1), ABA2, and third ABA in adulthood (ABA3). Their wheel running correlated with anxiety-like behavior. During ABA1 and ABA3, weight gain of Vx3 females (but not males) after food consumption correlated negatively with food-anticipatory activity (FAA) preceding the feeding hours, indicating that females with higher levels of running restrict feeding more and persistently. This paradoxical relationship confirms earlier findings of ABA females without ketamine treatment, capturing the maladaptive behaviors exhibited by individuals diagnosed with anorexia nervosa. By contrast, 30mgKetx3 had an effect on both sexes of reducing hyperactivity during the feeding hours acutely and reducing anxiety-like behavior's contribution to running. For females, only, 30mgKetx3 acutely improved the extent of compensatory food consumption relative to FAA and improved weight retention during ABA3, 12 days post ketamine in adulthood.