Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice
Year: 2024
Type: preprint
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.
Institutions: Stanford University, Stanford Medicine
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Institutes of Health
Awards: Modulation of protracted opioid withdrawal by dorsal raphe dynorphin neurons, Lightsheet Microscope for Large-Scale Imaging of Cleared Tissue Samples, Neural circuitry and synaptic physiology underlying MDMA's prosocial effect, Mapping Neural Circuit Activity Mediating MDMA's Prosocial Effect, Neural circuit dynamics of drug action:revealing, uncoupling, and restoring altered brain states
OpenAlex ID: W4392520252