Sex differences in the effect of bupropion and naltrexone combination on alcohol drinking in mice.
Pharmacol Biochem Behav
; 181: 28-36, 2019 06.
Article
in En
| MEDLINE
| ID: mdl-30991059
ABSTRACT
A fixed dose combination of bupropion (BPP) and naltrexone (NTX), Contrave®, is an FDA approved pharmacotherapy for the treatment of obesity. A recent study found that combining BPP with low-dose NTX reduced alcohol drinking in alcohol-preferring male rats. To explore potential pharmacological effects of the BPPâ¯+â¯NTX combination on alcohol drinking, both male and female C57Bl/6J mice were tested on one-week drinking-in-the dark (DID) and three-week intermittent access (IA) models. Neuronal proopiomelanocortin (POMC) enhancer knockout (nPE-/-) mice with hypothalamic-specific deficiency of POMC, and its bioactive peptides melanocyte stimulating hormone and beta-endorphin, were used as a genetic control for the effects of the BPPâ¯+â¯NTX. A single administration of BPPâ¯+â¯NTX (10â¯mg/kgâ¯+â¯1â¯mg/kg) decreased alcohol intake after DID in C57Bl/6J males, but not females. Also in C57Bl/6J males, BPPâ¯+â¯NTX reduced intake of the caloric reinforcer sucrose, but not the non-caloric reinforcer saccharin. In contrast, BPPâ¯+â¯NTX had no effect on alcohol DID in nPE-/- males. Pretreatment with the selective melanocortin 4 receptor (MC4R) antagonist HS014 reversed the anti-dipsogenic effect of BPPâ¯+â¯NTX on alcohol DID in C57Bl/6J males. In the 3-week chronic IA model, single or repeated administrations for four days of BPPâ¯+â¯NTX reduced alcohol intake and preference in C57Bl/6J males only. The behavioral measures observed in C57Bl/6J mice provide clear evidence that BPPâ¯+â¯NTX profoundly reduced alcohol drinking in males, but the doses tested were not effective in females. Furthermore, our results suggest a hypothalamic POMC/MC4R-dependent mechanism for the observed BPPâ¯+â¯NTX effects on alcohol drinking in male mice.
Key words
Full text:
1
Database:
MEDLINE
Complementary Medicines:
Homeopatia
Main subject:
Alcohol Drinking
/
Bupropion
/
Alcoholism
/
Drug Evaluation, Preclinical
/
Naltrexone
Type of study:
Prognostic_studies
Language:
En
Journal:
Pharmacol Biochem Behav
Year:
2019
Type:
Article