Aerobic Exercise Improves Food Reward in Obesity-prone Rats:Mediated by CP-AMPARs of Nucleus Accumbens

Objective:To explore the mechanism of nucleus accumbens calcium permeable AMPARs (CP-AMPARs) in improving food reward of obesity-prone rats by aerobic exercise.Methods:Sixty male SD rats were randomly divided into two groups:normal diet group (C,n=15) and high-fat diet group (HFD,n=45).After 8 weeks,the obesity-resistance group (OR,n=15) and obesity-prone group (OP,n=15) were selected from HFD.Then,OR and OP groups were divided into obesity-resistant control group (ORC,n=7)and obesity-resistant exercise group (ORE,n=7),obesity-prone control group (OPC,n=7) and obesity-prone exercise group (OPE,n=7),respectively.ORE rats and OPE rats were conducted a 6-week treadmill exercise intervention (50 min/time,6 times/week,starting speed 14 m/min,increasing 2 m/min per week),and instrumental conditioning test and conditioned place preference test were used to evaluate feeding motivation and food reward of rats.By observing the feeding behavior changes of rats after injection of 1-Naphthyl acetyl spermine (NASPM)(20μg/0.5μL),a selective antagonist of CP-AMPARs,the role of nucleus accumbens CP-AMPARs in motor regulation of eating behavior was evaluated.The local field potentials (LFPs) and neuronal activities in the nucleus accumbens were measured by in vivo multichannel electrophysiological technique.Western blotting and immunofluorescence double-labeling technique were used to detect the protein expression of GluA1 and GluA2 in the nucleus accumbens.Results:Compared with OR rats,the feeding motivation of OP rats was increased (P<0.01,P<0.05),but the feeding motivation of OPE rats was decreased (P<0.05).The NASPM injection decreased OPE rats feeding motivation more significantly than OPC rats (P<0.05)the number of GluA1,GluA2 positive cells and their co-expression positive cells and the ratio of GluA1 to GluA2 on the surface of the nucleus accumbens membrane were decreased (P<0.05).Furthermore,compared with ORC rats,the LFPs power spectral density in theta band of the nucleus accumbens of OPC rats (P<0.01),the mean discharge frequency of MSNs (P<0.01) and the Spike-LFPs coherence value were increased (P<0.01);however,the above variables of OPE rats was decreased compared with OPC rats (P<0.01).Conclusion:6-week aerobic exercise intervention could improve food reward,decrease feeding motivation,and delay weight gain in OP rats.The mechanism may be related to aerobic exercise changing the expression of GluA1∶GluA2 on the surface of nucleus accumbens membrane and decreasing CP-AMPARs synaptic insertion,the abnormal synchronous activity of Spike-LFPs is related to the regulation of nucleus accumbens MSNs.