Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice.
Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach, Daniel Ryskamp Rijsketic, Austen B Casey, Nicholas Gregory, Juliana S Salgado, Robert C. Malenka, Boris D. Heifets
bioRxiv : the preprint server for biology March 6, 2024 preprint DOI: 10.1101/2024.03.03.583196 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Mice |
| Interventions | ketamine naltrexone |
| Topics | Ketamine Esketamine |
| Keywords | Psychopharmacology Brain research Mental health |
| Citations | 1 |
| Key findings | Mu-opioid receptors in the central amygdala gate the locomotor effects of ketamine in mice, but are not direct targets of ketamine. |
Abstract
Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. It is unclear whether naltrexone blocks a direct effect of ketamine at ORs, or whether normal functioning of the OR system is required to realize the full antidepressant effects of treatment. In mice, the effect of ketamine on locomotion, but not analgesia or the forced swim test, was sensitive to naltrexone and was therefore used as a behavioral readout to localize the effect of naltrexone in the brain. We performed whole-brain imaging of cFos expression in ketamine-treated mice, pretreated with naltrexone or vehicle, and identified the central amygdala (CeA) as the area with greatest difference in cFos intensity. CeA neurons expressing both μOR (MOR) and PKCμ were strongly activated by naltrexone but not ketamine, and selectively interrupting MOR function in the CeA either pharmacologically or genetically blocked the locomotor effects of ketamine. These data suggest that MORs expressed in CeA neurons gate behavioral effects of ketamine but are not direct targets of ketamine.
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
Cites 21
- 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 Journal of Neuroscience April 15, 1997
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
- Deep posteromedial cortical rhythm in dissociation Nature September 16, 2020
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
and 16 more in the library