Impact of Roux‐en‐Y gastric bypass surgery on appetite, alcohol intake behaviors, and midbrain ghrelin signaling in the rat

Abstract

Objective Roux en Y Gastric Bypass surgery (RYGB) reduces appetite and stimulates new onset alcohol misuse, however the genesis of these behavioral changes is unclear. We hypothesized that new onset alcohol intake is a behavioral adaptation that occurs secondary to reduced appetite and correlates with altered central ghrelin signaling. Methods We evaluated hedonic high fat diet (HFD) intake prior to assessing alcohol intake behaviors in RYGB and control rats. We also measured circulating ghrelin, and ghrelin receptor (GHSR) regulation of neuronal firing in ventral tegmental area (VTA) dopamine (DA) neurons. Results RYGB rats displayed reduced HFD intake relative to controls. Sham and RYGB rats consumed more alcohol and preferred lower concentrations of alcohol whereas only RYGB rats escalated alcohol intake during acute withdrawal. Remarkably, GHSR activity, independent of peripheral ghrelin release, set the tonic firing tone of VTA DA neurons, a response selectively diminished in RYGB rats. Conclusions This study indicates that gut manipulations lead to increased alcohol intake whereas RYGB promotes behaviors that may maintain alcohol misuse. Reductions in hedonic feeding and diminished GHSR control of VTA firing further distinguish gut manipulation from complete bypass and present a potential mechanism linking reduced appetite with alcohol misuse after RYGB surgery.

Roux‐en‐Y gastric bypass surgery normalizes dopamine D1, D2, and DAT levels

“…Ghrelin antagonists have been shown to decrease alcohol reward in rats before (Jerlhag et al, ) and after RYGB (Hajnal et al, ). Only RYGB rats were found to increase alcohol intake during acute withdrawal and were found to have higher breakpoint in operant tasks (Hajnal et al, ; Sirohi, Richardson, Lugo, Rossi, & Davis, ). Vertical sleeve gastrectomy is another common surgical option for the treatment of obesity.…”

Vertical Sleeve Gastrectomy Attenuates Hedonic Feeding Without Impacting Alcohol Drinking in Rats

“…Specifically, RYGB surgery increases sensitivity, consumption, and motivation to obtain alcohol in rats that are nonalcohol preferring at baseline. Moreover, we recently discovered that this phenomenon occurred at the expense of reduced hedonic feeding , i.e., RYGB rats that displayed increased alcohol intake also selectively reduced hedonic intake of palatable food after a caloric preload. To determine whether surgical effects on alcohol extend to the VSG procedure, we examined alcohol intake over a range of alcohol concentrations.…”

“…Previous work from our group and others has indicated that RYGB surgery increases alcohol intake in rodents. Specifically, RYGB surgery increases sensitivity, consumption, and motivation to obtain alcohol (9)(10)(11) in rats that are nonalcohol preferring at baseline. Moreover, we recently discovered that this phenomenon occurred at the expense of reduced hedonic feeding (11), i.e., RYGB rats that displayed increased alcohol intake also selectively reduced hedonic intake of palatable food after a caloric preload.…”

“…The current study tested corollaries of the central hypothesis that adaptations in feeding behavior and hypothalamic gene expression contribute to body weight loss following VSG. Separate from feeding behavior, other bariatric techniques, namely Roux‐en‐Y gastric bypass (RYGB) surgery, stimulate new‐onset alcohol intake . We recently discovered that RYGB rats increased alcohol intake at the expense of palatable food intake, suggesting that surgery‐induced changes in appetite and alcohol intake may be causal .…”

Interactions Between Alcohol and the Endocannabinoid System

“…Interestingly, vagal afferent nerve firing is decreased by signals that increase alcohol intake, such as ghrelin (Date et al, 2002), whereas it is increased by blockade of peripheral ghrelin receptors (Kong et al, 2016) or by cholecystokinin (Date et al, 2002; Schwartz et al, 1997), which also reduces alcohol intake (Geary et al, 2004). The apparent reciprocal relationship between vagal afferent nerve firing and alcohol preference is compatible with the increased incidence of alcoholism following Roux‐en‐Y gastric bypass surgery, which disrupts gastric innervation (Hajnal et al, 2012), and results in loss of ghrelin regulation of the firing of VTA dopaminergic neurons (Sirohi et al, 2017).…”