The endogenous opioid system in the medial prefrontal cortex mediates ketamine's antidepressant-like actions.
Transl Psychiatry
; 14(1): 90, 2024 Feb 12.
Article
in En
| MEDLINE
| ID: mdl-38346984
ABSTRACT
Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions of ketamine and their molecular correlates in the medial prefrontal cortex (mPFC) are blocked by acute systemic administration of naltrexone, a competitive opioid receptor antagonist. Naltrexone delivered directly into the mPFC similarly disrupts the behavioral effects of ketamine. Ketamine treatment rapidly increases levels of ß-endorphin and the expression of the µ-opioid receptor gene (Oprm1) in the mPFC, and the expression of gene that encodes proopiomelanocortin, the precursor of ß-endorphin, in the hypothalamus, in vivo. Finally, neutralization of ß-endorphin in the mPFC using a specific antibody prior to ketamine treatment abolishes both behavioral and molecular effects. Together, these findings indicate that presence of ß-endorphin and activation of opioid receptors in the mPFC are required for the antidepressant-like actions of ketamine.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ketamine
Limits:
Animals
Language:
En
Journal:
Transl Psychiatry
Year:
2024
Document type:
Article
Affiliation country: