Hamilton John, Swenson Sabrina, Hajnal Andras, Thanos Panayotis K
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, New York.
Department of Psychology, University of Buffalo, Buffalo, New York.
Synapse. 2018 Jul 10. 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. [ 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.
Roux-en-Y胃旁路手术(RYGB)是治疗病态肥胖最有效的方法之一。然而,临床上观察到RYGB术后药物滥用有所增加。本研究检测了RYGB对多巴胺系统的影响,以阐明这些在奖赏相关行为中观察到的变化。将大鼠分为四组:假手术+正常饮食组、假手术+高脂(HF)自由饮食组、假手术+限制HF饮食组以及RYGB手术+HF饮食组。手术后,大鼠在各自的饮食条件下饲养9周后处死。进行[³H]SCH 23390、[³H]螺哌隆和[³H]WIN35 428放射自显影,以量化饮食和RYGB手术对1型多巴胺受体(D1R)样、2型多巴胺受体(D2R)样和多巴胺转运体(DAT)结合的影响。长期食用HF饮食的大鼠变得肥胖,腹外侧纹状体和伏隔核核心内的D1R样结合减少,纹状体所有区域以及伏隔核核心和壳内的D2R样结合减少,背内侧纹状体内的DAT结合减少。限制HF饮食的大鼠D1R样和D2R样结合的减少与肥胖大鼠相似,纹状体所有区域的DAT结合减少。RYGB组和限制HF饮食组大鼠体重减轻相似,RYGB组大鼠与对照组相比结合无差异。未治疗的肥胖大鼠和RYGB大鼠之间观察到的结合变化表明,RYGB逆转了HF饮食对多巴胺系统的影响。