Mechanisms underlying sustained resilience against anorexia nervosa from sub-anesthetic ketamine: A review and new research based on electron microscopic analyses of synapses using a mouse model.
Physiology & behavior September 1, 2025 Yiru Dong, Sebastian Goodwin-Groen, Jessie Ma et al. 4 citations
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.