High Fequency Stimulation Of Nucleus Accumbens For Treatment Of Obesity In Rats

Obesity is considered to be caused by energy intake exceeding energyexpenditure and consequently redundant adipose stored in tissue. Due to the nucleusaccumbens (NAc)’s inhibitory regulation in feeding behaviors and the excitationeffect of high frequency stimulation (HFS) on the neural activity, HFS of NAc mayreinforce its inhibitory regulation of feeding behavior, which consequentlycontributes to treatment of obesity. In order to prove our hypothesis, we successfullyestablished the obesity rates by feeding with high-fat food. Based on the animalmodel, high frequency stimulation (HFS) was used to observe behavioral effect inorder to verify the effectiveness of HFF in the treatment of obesity and then we alsostudied the possible mechanisms involved.Behavioral study:1.Effectiveness of nucleus accumbens (NAc) of HFS in thetreatment of rat obesity: In this part, we applied HFS to obese rats and it was foundthat the body weight growth rate decreased more prominently in Acb-Sh HFS groupthan in Acb-Sh sham HFS group. We could conclude that HFS in Acb-Sh might be apromising method to treat obesity.2. Effective target of HFS. It was found that HFSin the shell subregion of NAc (Acb-Sh) decreased the daily food intake in the obesityrats, while sham HFS in Acb-Sh could not. In contrast, no difference was observedbetween obesity rats with HFS in the core subregion of the NAc (Acb-Co) and theones with sham HFS in the Acb-Co. Therefore, the results indicates that the effectivestimulation target for the treatment of obesity is Acb-Sh rather than Acb-Co. Possible mechanisms study:1. qPCR experiment. In this study, we found that inthe obesity rats, the dopamine D2receptor expression was upregulated by HFS inAcb-Sh, while no such change was found in Acb-Co. In addition, dopamine D1receptor expression had no significant change after HFS was applied in both Acb-Shor in Acb-Co. The results indicates that upregulation of D2receptor rather than D1receptor expression in Acb-Sh is involved in the mechanism of therapeutic effect;2.Neurotransmitter microdialysis experiment. During the period of HFS in Acb-Sh,GABA levels increased in its projection nucleus including LH, VP and VTA,meanwhile DA level in the Acb-Sh increased. Accordingly, we postulate that HFSreinforces the neurons GABA outflow of Acb-Sh, to its target neurons, which may bethe principal mechanism of HFS action;3. Neuroelectrophysiological experiment:The discharge rate of neurons in the Acb-Sh and their target nucleus decreased duringthe period of HFS in Acb-Sh, which suggests that HFS in Acb-Sh suppressed thespontaneous neural activity in itself and its target nuclei. The results contributed tothe therapeutic effect of HFS.In conclusion, our studies in this project confirmed the possibility that HFS ofAcb could treat obesity. What’s more, the mechanism involved in the therapeuticeffect is also studied and the results display as following:1. HFS in Acb-Shreinforces the its synaptic GABA outflow to target neurons in LH, VP and VTA,consequently inhibits their neural activity, through which HFS strengthens theinhibitory role in regulation of feeding behavior;2. HFS upregulates the dopamineD2receptor expression in Acb-Sh, subsequently reinforces the inhibitory role ofreward system to control feeding behavior.