Contrave® is an adjunct pharmacotherapy for obesity that contains bupropion 
(BUP) and naltrexone (NTX). To further explore the psychopharmacology of this 
drug combination, male Sprague-Dawley rats were implanted with subcutaneous 
osmotic mini-pumps releasing: 40 mg/kg/day BUP, 4 mg/kg/day NTX, or 
40 + 4 mg/kg/day BUP and NTX (BN). During 12 days of exposure, the animals were 
tested on operant intraoral self-administration (IOSA) of high fructose corn 
syrup (HFCS) on continuous (FR1) and progressive ratio (PR) schedules, on home 
cage drinking of HFCS, and on HFCS taste reactivity. Locomotion activity was 
also assessed. At the conclusion of the study, mRNA expression of genes involved 
in reward processing, appetite and mood were quantified. It was found that BN 
produced effects that could largely be ascribed to either BUP or NTX 
independently. More specifically, BN-induced reductions of HFCS IOSA on a FR1 
schedule and home cage drinking, as well as alterations of MOR and POMC mRNA in 
the nucleus accumbens core and hypothalamus respectively, were attributable to 
NTX; while alterations of hippocampal BDNF mRNA was attributable to BUP. But, 
there was also some evidence of drug synergy: only BN caused persistent 
reductions of HFCS IOSA and drinking; BN produced the least gain of body weight; 
and only BN-treated rats displayed altered D2R mRNA in the caudate-putamen. 
Taken together, these observations support the use of BUP + NTX as a mean to 
alter consumption of sugars and reducing their impact on brain systems involved 
in reward, appetite and mood.