Bupropion and naltrexone combination alters high fructose corn syrup self-administration and gene expression in rats

Levy, AnneMarie; Daniels, Stephen; Hudson, Roger; Horman, Thomas; Flynn, Amanda; Zhou, Yan; Leri, Francesco

doi:10.1016/j.neuropharm.2018.01.035

Cited by 9 publications

(12 citation statements)

References 53 publications

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“…This low-dose combination of BPP+NTX with short-period treatments of 4 days did not change the body weight in either male or female mice, consistent with several prior reports showing that BPP+NTX did not reduce body weight in rats after relatively chronic administrations [Wright and Rodgers, 2013;Levy et al, 2018;Nicholson et al, 2018].…”

Section: Effects Of Single or Repeated Administrations Of Bpp+ntx (10supporting

confidence: 91%

“…Bupropion hydrochloride and naltrexone-hydrochloride (Sigma Aldrich, USA) or HS014 (Tocris, USA) were dissolved in 0.9% saline and administered within a range of doses known to affect alcohol drinking or food consumption in rodents [Greenway et al, 2009;Zhou et al, 2017a;Levy et al, 2018]. The BPP+NTX combination was studied at a ratio of 10 BPP/1 NTX in most experiments to model the ratio employed in Contrave® [Greenway et al, 2009].…”

Section: Methodsmentioning

confidence: 99%

“…Then alcohol was presented 10 min later and then alcohol intake values were recorded. The doses of the BPP +NTX combinations, BPP and NTX doses were suggested by the publications on rodent studies [Rhodes et al, 2005;Greenway et al, 2009;Wright and Rodgers, 2013;Zhou et al, 2017aZhou et al, , 2017bLevy et al, 2018]. Based on our preliminary results, the best combination of BPP (10 mg/kg) with sub-effective doses of NTX (1 mg/kg) was further studied in all the following experiments.…”

Section: Effects Of Single Bpp+ntx Bpp or Ntx Administration On Alcoholmentioning

confidence: 99%

“…It is known that obese individuals treated with this BPP+NTX combination have less cravings for palatable foods, and more control over their drive to consume food [Greenway et al, 2010]. Similarly, in rats, the reduction of food consumption by BPP+NTX was observed when the BPP+NTX was administered systemically or infused directly into the ventral tegmental area of male rats [Billes et al, 2014;Levy et al, 2018]. BPP (dopamine and norepinephrine reuptake inhibitor and nicotine receptor antagonist) is an antidepressant and smoking cessation agent, while NTX (a non-selective mu-opioid receptor [MOP-r] antagonist) is prescribed for both obesity and alcohol addiction [O'Malley et al, 1992[O'Malley et al, , 2002Greig and Keating, 2015;Karoly et al, 2015].…”

Section: Introductionmentioning

confidence: 97%

“…Hence, we determined the effect of BPP+NTX in a DID paradigm with limited access (4 h/day) and relatively low alcohol intake (<5-6 g/kg/day) which models "binge" drinking to the point of intoxication in mice [Rhodes et al, 2005;Zhou et al, 2017aZhou et al, , 2018. Because BPP+NTX increase proopiomelanocortin (POMC) expression and neuronal activity in the hypothalamus of rats [Greenway et al, 2009;Levy et al, 2018], we then investigated whether BPP+NTX could alter DID in neuronal POMC enhancer (nPE −/− ) knockout mice (with resultant loss of hypothalamic POMC) [Bumaschny et al, 2012;Lam et al, 2015], to explore potential neuronal mechanisms for the BPP+NTX effects. Two main neuropeptides beta-endorphin and melanocortin derived from POMC activate MOP-r and melanocortin receptors to increase and decrease alcohol consumption, respectively [Olney et al, 2014].…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in the effect of bupropion and naltrexone combination on alcohol drinking in mice

Zhou

Leri

Low

et al. 2019

Pharmacology Biochemistry and Behavior

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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 BPP+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 BPP +NTX. A single administration of BPP+NTX (10 mg/kg+1 mg/kg) decreased alcohol intake after DID in C57Bl/6J males, but not females. Also in C57Bl/6J males, BPP+NTX reduced intake of the caloric reinforcer sucrose, but not the non-caloric reinforcer saccharin. In contrast, BPP+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 BPP+NTX on alcohol DID in C57Bl/6J males. In the 3-week chronic IA model, single or repeated administrations for four days of BPP+NTX reduced alcohol intake and preference in C57Bl/6J males only. The behavioral measures observed in C57Bl/6J mice provide clear evidence that BPP+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 BPP+NTX effects on alcohol drinking in male mice.

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Section: Effects Of Single or Repeated Administrations Of Bpp+ntx (10supporting

confidence: 91%