Effects of the cannabinoid CB1-receptor neutral antagonist AM4113 and antagonist/inverse agonist rimonabant on fentanyl discrimination in male rats.
Drug Alcohol Depend
; 240: 109646, 2022 11 01.
Article
de En
| MEDLINE
| ID: mdl-36191533
ABSTRACT
Evidence suggests the existence of a functional interaction between endogenous cannabinoid (CB) and opioid systems. Thus, targeting CB1 receptors might be a viable approach to develop new medications for opioid use disorders (OUD). The present studies were undertaken to evaluate the effects of the neutral CB1 antagonist AM4113 and the CB1 antagonist/inverse agonist rimonabant in male rats trained to discriminate 0.032 mg/kg fentanyl from saline under a 10-response fixed-ratio (FR-10) schedule of food reinforcement. Results show that the µ-opioid agonists (fentanyl, oxycodone, and morphine) substituted fully and dose-dependently for fentanyl, whereas pretreatment with the µ-opioid antagonist naltrexone antagonized fentanyl's discriminative-stimulus effects. In interaction studies, AM4113 (0.32 or 1.0 mg/kg) was more effective in blocking fentanyl discrimination at 10-fold lower doses that did not modify rates of food-maintained responding, whereas rimonabant (1.0-10 mg/kg) produced some attenuation of fentanyl's discriminative-stimulus effects at the highest dose tested which also significantly decreased response rates. These results extend our recent work showing that AM4113 can effectively block the behavioral effects of heroin without producing rimonabant-like adverse effects. Taken together, these data suggests that CB1 neutral antagonists effectively block the behavioral effects of structurally distinct morphinan (heroin) and phenylpiperidine-based (fentanyl) opioids and may provide a novel therapeutic option for the treatment of OUD.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cannabinoïdes
/
Antagonistes des récepteurs de cannabinoïdes
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Drug Alcohol Depend
Année:
2022
Type de document:
Article
Pays d'affiliation:
Arabie saoudite