Neuro-hormonal mechanisms underlying changes in reward related behaviors following weight loss surgery: Potential pharmacological targets

Currently, the only available effective treatment option for obesity and its comorbidities is weight loss surgery (WLS). Long-term maintenance of weight loss after surgery cannot be explained by caloric restriction or malabsorption alone and has been attributed to unexplained changes in eating behavior. Whether these behavioral changes are related to altered taste or reward functions, or both, are subject to debate. In contrast to reduced food cravings and food addiction following WLS, recent clinical studies have revealed that bariatric surgery patients are prone to an increased risk for substance use disorder (SUD), especially alcohol use disorder (AUD). The substitution of drugs for previously stimulating foods, and the emergence of SUD after WLS, supported by preclinical studies, strongly suggest that manipulation of gut-brain signals may bring about changes in the reward system. This paper reviews current clinical and basic science research and discusses potential underlying mechanisms of reward-related behaviors. Specifically, it explores relevant neural and hormonal changes that present post WLS and their effects on dopaminergic reward pathway and highlights targets for potential pharmacological interventions. Special emphasis is given to recent work suggesting that different types of WLS procedures such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have differential effects on alcohol consumption in humans and rats. These differential effects may hold the key not only to understanding increased substance use following WLS but may also help elucidate the contribution of gut-brain signals to regulation of reward, in general.