Ketamine Responsiveness of Mice Exhibiting Anorexia-Like Behavior Correlates With Synaptic AMPA Receptor Distribution

Area of Science:

• Neuroscience
• Pharmacology
• Eating Disorders Research

Background:

• Anorexia nervosa (AN) is a severe eating disorder with high mortality.
• Activity-based anorexia (ABA) is a validated animal model for AN.
• Previous studies showed ketamine reduces relapse vulnerability in ABA models.

Purpose of the Study:

• To investigate if ketamine induces sustained changes in AMPA receptors (AMPARs) in the prefrontal cortex (PFC).
• To correlate these AMPAR changes with individual differences in sustained behavioral improvements in the ABA model.

Main Methods:

• Adolescent female mice underwent two cycles of ABA induction.
• Mice received either 30 mg/kg or 3 mg/kg of ketamine.
• Electron microscopy with immunogold localization was used to analyze AMPAR distribution in PFC synapses.

Main Results:

• Increased cytoplasmic AMPARs in pyramidal neuron (PN) synapses correlated with better body weight retention and reduced wheel running.
• Increased AMPARs in PN cytoplasm and GABA interneuron (GABA-IN) synapses were linked to higher food intake during recovery.
• Findings support a model where PFC circuitry modulation by ketamine promotes feeding and reduces hyperactivity.

Conclusions:

• Ketamine administration leads to sustained alterations in AMPARs within the PFC.
• These neuroplastic changes are associated with improved resilience against ABA-induced behaviors.
• Targeting PFC AMPARs may offer a therapeutic strategy for enhancing recovery from anorexia nervosa.