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

Roux-en-Y gastric bypass (RYGB) surgery reduces appetite and stimulates new onset alcohol misuse; however, the genesis of these behavioral changes is unclear. This study is hypothesized that new onset alcohol intake is a behavioral adaptation that occurs secondary to reduced appetite and correlates with altered central ghrelin signaling. Hedonic high-fat diet (HFD) intake was evaluated prior to the assessment of alcohol intake behaviors in RYGB and control rats. Measurements were also taken of circulating ghrelin and ghrelin receptor (GHSR) regulation of neuronal firing in ventral tegmental area (VTA) dopamine (DA) neurons. 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 of VTA DA neurons, a response selectively diminished in RYGB rats. 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.