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

• Published in: Synapse (New York, N.Y.) Vol. 72; no. 10
• Main Authors: Hamilton, John, Swenson, Sabrina, Hajnal, Andras, Thanos, Panayotis K.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2018
• Subjects: Amphetamines; Autoradiography; Diet; Dopamine; Dopamine D1 receptors; Dopamine D2 receptors; Dopamine transporter; Drug abuse; food restriction; Gastric bypass; Gastrointestinal surgery; Heart surgery; High fat diet; Neostriatum; Nucleus accumbens; Nutrient deficiency; Obesity; Reinforcement; reward deficiency syndrome; Rodents; RYGB; Spiperone; Surgery; food restriction; RYGB; reward deficiency syndrome; dopamine; high fat diet; obesity
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.22058

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. [3H]SCH 23390, [3H]Spiperone, and [3H]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. Using in vitro autoradiography, we demonstrate that Roux‐en‐Y gastric bypass surgery helps normalize changes in dopamine receptors and transporters seen after high fat diet in rats. These results may help shed light on the inconsistencies found in the literature regarding the effects of RYGB surgery on dopamine signaling.