title: Deep brain stimulation of the nucleus accumbens shell induces anti-obesity effects in obese rats with alteration of dopamine neurotransmission.
abstract: The aim of this study was to assess the anti-obesity effects of nucleus accumbens shell (NAc-sh) deep brain stimulation (DBS) in diet-induced obese (DIO) and chow-fed (chow) rats. The influence of DBS on dopamine (DA) signaling in the NAc-sh was also evaluated. DIO and chow rats were subjected to DBS for 14 consecutive days. Food intake and weight gain were measured daily. The gene expression of the dopamine D1 and D2 receptors was evaluated by qPCR. In addition, the extracellular levels of DA and its metabolite, dihydroxyphenylacetic acid (DOPAC), were determined by microdialysis. We observed that chronic DBS induced significant reductions in total energy intake (596.0±65.0kcal vs. 1161.6±22.2kcal, p<0.001) and weight gain (1.45±0.57% vs. 9.64±0.38%, p<0.001) in DIO rats compared to sham-DIO rats. Up-regulated D2 receptor gene expression (2.43±0.12 vs. 0.64±0.04, p<0.001) and increased DA levels (2.73±0.15pmol/mL vs. 0.62±0.05pmol/mL, p<0.001) were observed in DIO rats compared to sham-DIO rats. DBS had no influence on food intake, weight gain, or DA neurotransmission in chow rats. Our results support an association of the anorexigenic effects of NAc-sh DBS with mesolimbic DA signaling and indicate that the positive alteration of DA function in DIO rats may be responsible for the different effects of DBS in DIO and chow rats.
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Beijing 100050, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Hospital of Lanzhou University, Chengguan District, Lanzhou, Gansu, 730030, China.
authors.forename: Nai-Li
authors.initials: NL
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Beijing 100050, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Beijing 100050, China. Electronic address: zhangkai62035@163.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D046690:Deep Brain Stimulation; D004298:Dopamine / Q000378:metabolism*; D004435:Eating; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism / Q000503:physiopathology*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D009435:Synaptic Transmission; D015430:Weight Gain
chemical_list: D017447:Receptors, Dopamine D1; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine
keywords: Deep brain stimulation; Dopamine; Nucleus accumbens shell; Obesity