Center for Neural Science, New York University, 4 Washington Place, New York, NY 10003, USA; Neuroscience Institute, NYU Langone, New York, NY 10003, USA. Electronic address: ca3@nyu.edu.
2 papers in the library · 6 citations · publishing 2025
Repeated exposure to the activity-based anorexia (ABA) animal model, which mimics key features of anorexia nervosa such as starvation-induced hyperactivity and severe weight loss, can build resilience against relapse through synaptic changes. Sub-anesthetic ketamine given during mid-adolescence enhances this resilience. At medial prefrontal cortex synapses, ketamine increases GluN2B-containing NMDA receptors and the F-actin binding protein drebrin at excitatory synapses on pyramidal cells and GABA-interneurons. These molecular changes occur near 15 days post-injection during relapse in late adolescence. Ketamine treatment in late adolescence also reduces ABA relapse in adulthood, though less effectively. Wheel running promotes inhibitory GABAergic synapse formation on hippocampal pyramidal cells, and ketamine augments this inhibition, suppressing starvation-evoked hyperactivity and increasing food consumption and weight gain.
Anorexia nervosa (AN) has no approved medication and a high relapse rate, especially among adult women. Ketamine infusions have been linked to sustained remission in some adult women with severe AN, and prior mouse studies showed ketamine reduced vulnerability to activity-based anorexia (ABA) in adolescent mice. This experiment tested ketamine in adult female mice undergoing three ABA cycles. Severe weight loss during the third cycle occurred in 89% of control mice but only 69% of ketamine-treated mice. Ketamine significantly reduced overall daily wheel running during the second ABA cycle, including during food availability, and this reduction persisted into the third cycle 10–13 days later. Food intake was not significantly changed. Ketamine may reduce relapse vulnerability in adult females by curbing excessive activity.