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

Abstract

Roux-en-Y gastric bypass surgery (RYGB) is one of the most effective treatments for morbid obesity. However, increased substance abuse following RYGB has been observed clinically. This study examined the effects of RYGB on the dopamine system to elucidate these observed changes in reward-related behavior. Rats were assigned to four groups: normal diet with sham surgery, ad libitum high fat (HF) diet with sham surgery, restricted HF diet with sham surgery, and HF diet with RYGB surgery. Following surgeries, rats were kept on their respective diets for 9 weeks before they were sacrificed. [ H]SCH 23390, [ H]Spiperone, and [ H]WIN35 428 autoradiography was performed to quantify the effects of diet and RYGB surgery on dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and dopamine transporter (DAT) binding. Rats on a chronic HF diet became obese with reduced D1R-like binding within the ventrolateral striatum and the nucleus accumbens core, reduced D2R-like binding in all areas of the striatum and nucleus accumbens core and shell, and reduced DAT binding in the dorsomedial striatum. Restricted HF diet rats showed similar reductions in D1R-like and D2-R-like binding as the obese rats, and reduced DAT binding within all areas of the striatum. Both RYGB and restricted HF diet rats showed similar weight reductions, with RYGB rats showing no difference in binding compared to controls. The observed changes in binding between non-treated obese rats and RYGB rats demonstrates that HF dietary effects on the dopamine system were reversed by RYGB.

Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors

“…While it is true that the major body of the RDS concept resides in many publications on the subject from our laboratory, there is an emerging increase in independent citations that embrace this novel construct. A brief sampling of this global cited work, while mostly favorable, can be assessed by reviewing specific references [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ,…”

Roux-en-Y gastric bypass in rat reduces mu-opioid receptor levels in brain regions associated with stress and energy regulation

“…It has also been reported that MOR inhibition in the lateral hypothalamus, but not the nucleus accumbens or ventral tegmental area, reduces food intake in food-deprived mice, suggesting that opioid signaling in the hypothalamus mediates hunger rather than the rewarding aspect of food consumption [39]. Our laboratories previously reported that body weight significantly decreases in the 8 weeks following RYGB surgery [34] (Fig 3). The reduction in hypothalamus [ 3 H] DAMGO binding seen between the high-fat fed Sham-FR and RYGB groups suggests that decreased body weight may be due to decreased hunger driven by downregulated mu opioid signaling in this region.…”

“…We previously reported that dopamine receptor expression decreases in the nucleus accumbens and striatum of high-fat diet-fed rats, and returns to control levels following RYGB surgery [34]. Increased dopamine signaling in this region can facilitate reward-seeking behavior including food and drug intake [68].…”

“…Recently, our laboratories reported that changes in the dopamine system induced by a high-fat diet are reversed by RYGB [34]. Dopamine receptor binding decreased in the striatum and nucleus accumbens of rats fed a high-fat diet, while RYGB rats showed no difference in binding compared to standard diet controls, indicating that RYGB reverses the dopamine system changes induced by the high-fat diet.…”

Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation

“…In obese people, the availability of striatal dopaminergic D2R is reduced ( Wang et al, 2001 ), while several prefrontal cortex regions are overactivated upon meal consumption or exposure to food cues ( Tomasi and Volkow, 2013 ) (for review Volkow et al, 2011 ). Conversely, RYGB reduces prefrontal cortex activation and may restore striatal D2R availability ( Hamilton et al, 2018 ). In summary, postingestive sugar sensing is important for body homeostasis as well as sweet gustation, but the exact mechanisms underlying post-oral learned sugar preference still need to be elucidated.…”