Purpose Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for morbid obesity. Increased alcohol abuse after RYGB resulted in recommendations to exclude patients with alcohol abuse histories from RYGB. The purpose of our study was to examine the effects of a RYGB on ethanol intake in diet-induced obese rats (high-fat diet). Methods Animals underwent RYGB and were habituated along with their sham-operated obese controls and with lean rats to increasing concentrations of ethanol in a two-bottle choice paradigm. Results RYGB rats’ daily consumption of ethanol averaged 2 g/kg at 2% habituation and 3.8 g/kg at 4% habituation, twice as much as sham-operated obese controls and 50% more than normal-diet lean controls. Obese controls drank on average 1 g/kg of ethanol (2 and 4%), significantly less (50%) than lean controls. RYGB rats when given higher ethanol concentrations (6 and 8%) or no ethanol drank significantly more water than lean and obese controls (66 and 100% respectively) and their enhanced total fluid intake was associated with increased food intake, which was significantly higher than in lean (66% more calories; food + alcohol) and obese controls (44% more calories). The lower alcohol intake in the obese controls than in the lean rats suggests that obesity may interfere with alcohol’s rewarding effects and RYGB may remove this protective effect. Conclusions The overall enhancement of consummatory behaviors (both ethanol and water) suggests that RYGB may facilitate alcohol consumption, which in vulnerable individuals could lead to abuse and addiction.

BackgroundRoux-en-Y gastric bypass (RYGB) surgery is a very effective bariatric procedure to achieve significant and sustained weight loss, yet little is known about the procedure’s impact on the brain. This study examined the effects of RYGB on the brain’s response to the anticipation of highly palatable versus regular food.MethodsHigh fat diet-induced obese rats underwent RYGB or sham operation and were then tested for conditioned place preference (CPP) for the bacon-paired chamber, relative to the chow-paired chamber. After CPP, animals were placed in either chamber without the food stimulus, and brain-glucose metabolism (BGluM) was measured using positron emission tomography (μPET).ResultsBacon CPP was only observed in RYGB rats that had stable weight loss following surgery. BGluM assessment revealed that RYGB selectively activated regions of the right and midline cerebellum (Lob 8) involved in subjective processes related to reward or expectation. Also, bacon anticipation led to significant activation in the medial parabrachial nuclei (important in gustatory processing) and dorsomedial tegmental area (key to reward, motivation, cognition and addiction) in RYGB rats; and activation in the retrosplenial cortex (default mode network), and the primary visual cortex in control rats.ConclusionsRYGB alters brain activity in areas involved in reward expectation and sensory (taste) processing when anticipating a palatable fatty food. Thus, RYGB may lead to changes in brain activity in regions that process reward and taste-related behaviors. Specific cerebellar regions with altered metabolism following RYGB may help identify novel therapeutic targets for treatment of obesity.

Introduction Cocaine is a highly addictive drug of abuse for which there are currently no medications. In rats and mice d-cycloserine (DCS), a partial NMDA agonist, accelerates extinction of cocaine seeking behavior. Since cues delay extinction here, we evaluated the effects d-cycloserine in extinction with and without the presence of cues. Methods Two doses of DCS (15 and 30 mg/kg) were studied in C57 mice. Mice self-administered cocaine (1 mg/kg) for 2 weeks and then underwent a 20-day extinction period where DCS was administered i.p. immediately following each daily session. Extinction was conducted in some mice with the presence of cocaine-paired cues; while others were in the absence of these cues. Results DCS treated mice (either dose) showed significantly reduced lever pressing during extinction with cue exposures when compared with vehicle treated mice. Without cues, animals showed much lower levels of lever pressing but the differences between vehicle and DCS were not significant. Conclusion DCS accelerated extinction with the presence of cues, but there were no differences on extinction without cues as compared with vehicle. These findings are consistent with DCS disrupting the memory process associated with the cues. Since drug cues are significantly involved in relapse, these findings support research to assess the therapeutic potential of DCS in cocaine addiction.†

Expectation of salient rewards and novelty seeking are processes implicated in substance use disorders but the neurobiological substrates underlying these associations are not well understood. To better understand the regional circuitry of novelty and reward preference, rats were conditioned to pair unique cues with bacon, an initially novel food, or chow, a familiar food. In the same animals, after training, cue-induced brain activity was measured, and the relationships between activity and preference for three rewards, the conditioned foods and ethanol (EtOH), were separately determined. Activity in response to the food paired-cues was measured using brain glucose metabolism (BGluM). Rats favoring bacon-paired (BAP) cues had increased BGluM in mesocorticolimbic brain regions after exposure to these cues, while rats favoring chow-paired (CHP) cues showed relative deactivation in these regions. Rats exhibiting BAP cue-induced activation in prefrontal cortex (PFC) also consumed more EtOH while rats with cortical activation in response to CHP cues showed lower EtOH consumption. Additionally, long-term stable expression levels of PFC Grin2a, a subunit of the NMDA receptor, correlated with individual differences in EtOH preference insomuch that rats with high EtOH preference had enduringly low PFC Grin2a mRNA expression. No other glutamatergic, dopaminergic or endocannabinoid genes studied showed this relationship. Overall, these results suggest that natural variation in mesocorticolimbic sensitivity to reward-paired cues underlies behavioral preferences for and vulnerability to alcohol abuse, and support the notion of common neuronal circuits involved in food- and drug-seeking behavior. The findings also provide evidence that PFC NMDA-mediated glutamate signaling may modulate these associations.