Individual differences in the positive outcome from adolescent ketamine treatment in a female mouse model of anorexia nervosa involve drebrin A at excitatory synapses of the medial prefrontal cortex
Rose Temizer, Yi‐Wen Chen, Chiye Aoki
Synapse September 19, 2022 DOI: 10.1002/syn.22253 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model study Peer reviewed |
|---|---|
| Population | Adolescent female mice in an activity-based anorexia model |
| Intervention | Ketamine |
| Dose | 30 mg/kg and 3 mg/kg |
| Topics | Esketamine Ketamine |
| Key points | A single 30 mg/kg ketamine injection, but not 3 mg/kg, produced lasting reductions in anorexia-like symptoms in adolescent female mice, with individual variability in response. Electron microscopy linked the higher dose to greater excitatory synapse density on GABAergic interneurons and a higher proportion of drebrin A-positive excitatory synapses on pyramidal neurons and interneurons, which the authors interpret as evidence of ketamine-induced homeostatic plasticity involving drebrin A. |
Abstract
Anorexia nervosa (AN) is a mental illness with the highest rates of mortality and relapse, and no approved pharmacological treatment. Using an animal model of AN, called activity‐based anorexia (ABA), we showed earlier that a single intraperitoneal injection of ketamine at a dose of 30 mg/kg (30mgKET), but not 3 mg/kg (3mgKET), has a long‐lasting effect upon adolescent females of ameliorating anorexia‐like symptoms through the following changes: enhanced food consumption and body weight; reduced running and anxiety‐like behavior. However, there were also individual differences in the drug's efficacy. We hypothesized that individual differences in ketamine's ameliorative effects involve drebrin A, an F‐actin‐binding protein known to be required for the activity‐dependent trafficking of NMDA receptors (NMDARs). We tested this hypothesis by electron microscopic quantifications of drebrin A immunoreactivity at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (GABA‐IN) in deep layer 1 of prefrontal cortex (PFC) of these mice. Results reveal that (1) the areal density of excitatory synapses on GABA‐IN is greater for the 30mgKET group than the 3mgKET group; (2) the proportion of drebrin A+ excitatory synapses is greater for both PN and GABA‐IN of 30mgKET than 3mgKET group. Correlation analyses with behavioral measurements revealed that (3) 30mgKET's protection is associated with reduced levels of drebrin A in the cytoplasm of GABA‐IN and higher levels at extrasynaptic membranous sites of PN and GABA‐IN; (5) altogether pointing to 30mgKET‐induced homeostatic plasticity that engages drebrin A at excitatory synapses of both PN and GABA‐IN.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- 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
- Subanesthetic Ketamine Ameliorates Activity-Based Anorexia of Adult Mice. Synapse 2025
- Ketamine Responsiveness of Mice Exhibiting Anorexia‐Like Behavior Correlates With Synaptic AMPA Receptor Distribution Synapse May 1, 2026
- Ketamine Sustains and Enhances the Protective Effects of a Ketogenic Diet Against Relapses in an Anorexia Mouse Model Hippocampus October 7, 2025
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and 17 more in the library