Regulation Of Nucleus Accumbens-lateral Hypothalamus GABA Neural Pathway On Hedonic Feeding In Rats

Objective:To explore the regulatory effects of the GABAergic neurons in nucleus accumbens(NAc)on palatable food(PF)intake via orexin-A expression in lateral hypothalamus(LHA)of the normal diet(ND)and diet-induced obesity(DIO)rats.Methods:The body weight of rats in normal diet group and high fat diet group were measured every week.Eight weeks later,6 ND rats and 6 DIO rats were randomly selected to observe the difference of palatable food intake between ND rats and DIO rats in 30 min.The nerve projections from GABA neurons in NAc to LHA neurons were observed by fluorescence gold retrograde tracing and fluorescence immunohistochemical staining.The expression of orexin-A and nesfatin-1 in LHA neurons and the co-expression of orexin-A and GABA-A receptors in LHA were observed by fluorescence immunohistochemistry,and the changes of GABAergic pathway from NAc to LHA in the DIO rats were observed.The effects of microinjection of GABA and electrical stimulation of NAc on the discharge activity of gastric dilatation(GD)sensitive neurons in LHA of ND and DIO rats were observed by single extracellular discharge method,and the effects of GABA-A receptor antagonist bicuculline(BIC)on this effect were also observed.Through microinjection of GABA-A receptor agonist muscimol(MUS)or GABA-A receptor blocker BIC into LHA and electrical stimulation of NAc,the effects of GABAergic signal in NAc on hedonic feeding in ND and DIO rats were observed,and the changes of palatable food intake after blocking orexin-A signal were observed.Results:1.The palatable food intake in the DIO rats was significantly higher than that of the ND rats(P < 0.05).2.After the palatable food intake,the nesfatin-1 expression was increased significantly in the LHA of the ND and DIO rats(P < 0.05),and orexin-A in LHA of ND rats decreased significantly(P < 0.05),while the orexin-A expression in DIO rats did not change significantly(P > 0.05).3.The results of fluorogold retrograde tracing combined with fluorescence immunohistochemistry showed that the number of FG and GABA coexisting neurons in NAc of DIO rats was significantly lower than that of ND rats(P < 0.05),while there was no significant difference in the number of orexin-A and GABA-A receptor double labeled immunopositive neurons in LHA of ND and DIO rats(P > 0.05).4.The effect of GABA in LHA on the discharge activity of gastric dilatation(GD)sensitive neurons showed that GABA administration by microelectrode could significantly reduce the discharge frequency of most GD excitatory neurons(GD-E)and GD inhibitory neurons(GD-I)in LHA of ND and DIO rats(P < 0.05),and the inhibitory effect of microinjection of GABA in LHA on GD neurons of DIO rats was more significant than that of ND rats(P < 0.05).Microinjection of GABA-A receptor antagonist BIC into LHA could partially block the inhibitory effect of GABA(P < 0.05).Electrical stimulation of NAc significantly increased the discharge frequency of GD-E and GD-I neurons in LHA(P < 0.05).When the BIC was pretreated in the LHA,the effect of electrical stimulation of NAc on GD sensitive neurons of ND rats was further increased(P < 0.05),while the effect of electrical stimulation of NAc on GD neurons of DIO rats did not change significantly after preadministration of BIC in the LHA(P >0.05).5.Microinjection of MUS into the LHA significantly decreased the intake of palatable food in ND and DIO rats(P < 0.05),and increased the intake of palatable food in ND rats by microinjection of BIC(P < 0.05),while there was no significant change in the intake of palatable food in the DIO rats(P > 0.05).After electrical stimulation of NAc,the palatable food intake of the ND rats was significantly decreased(P < 0.05),while the inhibitory effects of electrical stimulation NAc on palatable food intake was significantly weakened by microinjection BIC into the LHA(P < 0.05).The palatable food intake was remarkably decreased in DIO rats after the NAc electrical stimulation(P < 0.05),but there was no significant difference with the electrical stimulation group after microinjection of NS into LHA(P > 0.05).6.Intracerebroventricular injection of orexin-A receptor blocker SB334867,could significantly reduce the hedonistic food intake of rats(P < 0.05),while there was no remarkable difference in the palatable food intake after the pre-administration BIC into the LHA(P > 0.05).Conclusion:GABAergic signal of nucleus accumbens can regulate the expression of orexin-A in the LHA neurons and the intake of palatable food.The signal of GABAergic neural pathway between NAc and hypothalamic LHA in DIO rats was weakened,and orexin-A remained at a high level after intake of palatable food,which played a role in promoting food intake in DIO rats.Activation of GABA receptor in LHA or intracerebroventricular injection of orexin-A receptor antagonist can effectively reduce the palatable food intake of DIO rats.