Ketamine and Activity-Based Anorexia

Reviewed by Heather Dlugosz, MD, CEDS

Chen, Y. W., Sherpa, A. D., & Aoki, C. (2018). 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. International Journal of Eating Disorders, 51(8), 1020-1025.

https://doi.org/10.1002/eat.22937

Anorexia Nervosa has the highest mortality of any psychiatric illness (Crow et al. 2009), functional impacts that rival schizophrenia (Streigel-Moore et al. 2000) and is without any current FDA approved pharmacologic treatment options.  The importance of research focused in pharmacologic interventions to help treat Anorexia Nervosa is imperative.  In this study, researchers tested the effects of a single dose of Ketamine on female adolescent mice to developing activity based anorexia (ABA).  Activity based anorexia (ABA) is a model in animals that captures the key features of anorexia including excessive voluntary exercise, food restriction, weight loss severity and increased anxiety following weight recovery. Vulnerability to activity based anorexia can be quantified by increased wheel exercise activity following food restriction which contributes to weight loss and prolonged stress-induced anxiety-like behavior in recovered animals that have been fully weight restored.

Ketamine was selected in this study given it has recently received increased attention related to its reduction of acute suicidality following a single dose (Lee et al. 2015), quick antidepressant effects, and its anxiolytic effects in humans and animals (Yi-Wen Chen et al. 2018).  Ketamine works to non-competitively block the action of the N-Methyl-D-aspartate (NMDA) receptor found in never cells. In adolescent female mice exposed to activity based anorexia, there are brain changes in the regions that are involved in regulating anxiety including the dorsal and ventral hippocampus.  In the dorsal hippocampus, a mouse’s vulnerability to developing anxiety based anorexia based on weight loss correlates to increased levels of specific subunits of the NMDA receptor (Chen, Actor-Engel et al. 2017). In the study, researchers therefore, hypothesized whether a single dose of Ketamine could decrease vulnerability to the development of activity based anorexia based on the mechanism of action of Ketamine on the subunits of the NMDA receptor.

Adolescent female mice underwent activity based anorexia induction by exposing them to food restriction in mid adolescence followed by a recovery period and then food restriction again in late adolescence followed by a second recovery period. 2 varying doses of Ketamine (3 or 30mg) were administered once during the 1st period of food restriction.  They measured food consumption, body weight, wheel running activity daily and anxiety-like behaviors with a specialized maze test.

Results showed that the 30mg dose of Ketamine increased food intake compared to controls during the 1st restriction period, facilitated weight gain in the 1st period of recovery and in the 2nd restriction period increased food intake and weight gain in the feeding hours. At the end of the 2nd restriction period, the group receiving the higher dose of Ketamine showed marginally less weight loss compared to the controls. Both Ketamine groups also showed reduced wheel running activity compared to controls and reduced anxiety-like behaviors. In the second recovery period, both Ketamine groups gained more weight than the control group.

Why is This important?

This study demonstrates that a single higher dose of Ketamine supports a reduction in susceptibility to activity based anorexia exposure effects in female mice.  The observed effects of Ketamine create hope for its utility in supporting resilience to recurrence of activity based anorexia. With no current psychopharmacologic treatments for Anorexia Nervosa, positive studies like this one will encourage further research in humans.