Ketamine Responsiveness of Mice Exhibiting Anorexia‐Like Behavior Correlates With Synaptic AMPA Receptor Distribution
Synapse May 1, 2026 Bridget Xu, Cassandra Carrasco, Yi‐Wen Chen et al.
In adolescent female mice exposed to an activity-based anorexia model, a 30 mg/kg dose of ketamine reduced relapse vulnerability—measured as increased food intake, higher body weight, and reduced excessive wheel running—compared to a 3 mg/kg dose. Individual differences in responsiveness correlated with changes in AMPA receptors (AMPARs) in the prefrontal cortex. Greater AMPAR density in the cytoplasm of pyramidal neuron synapses was linked to better body weight retention and less hyperactivity during relapse. Higher AMPAR levels in both pyramidal neuron cytoplasm and GABA interneuron postsynaptic densities were associated with greater food intake during recovery. These findings suggest ketamine-induced synaptic changes in prefrontal circuits may promote resilience against anorexia relapse.