Orexin-A Affects Glucose Sensitive Neurons In The Nucleus Accumbens And Gastric Motility And Modulation By The Lateral Nucleus In Rats

Objective: To explore the effects and the potential regulation mechanisms of orexin-A and the neural pathways between lateral nucleus(LHA)and nucleus accumbens(NAcc)on electrical activity of glucose sensitive(GS)neurons in nucleus accumbens and gastric motility.Methods: Adult male wiatar rats were used,and randomly divided into three parts.We used retrograde tracing and fluorescent-immunohistochemistry staining method to observe the neural pathways between lateral nucleus(LHA)and nucleus accumbens(NAcc)in the first part of rats.Uesd the extracellular discharges of single unit neuron to identify glucose sensitive(GS)neurons in nucleus accumbens,and observe the change of discharge frequency of glucose sensitive neurons followed by nucleus accumbens microinjection of orexin-A,and the change of discharge frequency of glucose sensitive neurons activated by orexin-A in nucleus accumbens after electrical stimulated lateral nucleus in the two part of rats.We used gastric motility recording in vivo to observe the change of the amplitude and frequency of gastric constriction following by nucleus accumbens micinject differents leve ls of orexin-A,and the change of gastric motility after electrical stimulated lateral nucleus in the three part of rats.Results: Retrograde tracing and fluorescent –immunohistochemistry study shown that orexin-A/ fluorogold(FG)dual labelled neurons were found in the lateral nucleus.Electrophysiological study shown that 62 glucose sensitive(GS)neurons within the nucleus accumbens were recorded,of which 42 identified as GS-E neurons and 20 identified as GS-I neurons included.The discharge frequency of 30 of 42(30/42,71.43%)GS-E neurons were significantly rised(P < 0.05)and 10(10/42,23.81%)GS-E neurons were declined following microinjection of orexin-A into the nucleus accumbens.Out of the 20 GD-I neurons,15(15/20,75%)neurons excited by orexin-A(P < 0.05)while 4(4/20,20%)neurons were inhibited(P<0.05).After pre-injection of SB-334867 into the nucleus accumbens,the effects induced by orexin-A were abolished.After electrical stimulation to LHA,39 orexin-A sensitive GS-E neurons and 20 orexin-A sensitive GS-I neurons were recorded in the nucleus accumbens.In orexin-A sensitive GS-E neurons,the discharge frequency of 28(28/39,71.79%)neurons were further rised(P < 0.05)while 7(7/39,17.94%)neurons were declined(P < 0.05).In orexin-A sensitive GS-I neurons,the discharge frequency of 14(14/20,70%)neurons were significantly rised while 4 neurons were significantly weaken(P < 0.05).Pre-injection treatment with orexin-A receptor antagonist SB334867 in the nucleus accumbens,responses induced by electrical stimulation of the Pe F were both markly declined(P < 0.05).Gastric motility study illustrated that orexin-A microinject to the nucleus accumbens,the amplitude and frequency of gastric motility in rats were dose-dependently increased significantly(P < 0.05).SB-334867 microinject to the nucleus accumbens could block the effect on gastric contraction(P < 0.05).The amplitude and frequency of gastric motility were significantly enhanced after electrical stimulation of LHA in rats(P < 0.05).The effect on gastric motility included by orexin-A was disappeared or weaken following by SB-334867 microinject to the nucleus accumbens(P < 0.05).Conclusion: There exist the neural pathways between lateral nucleus and nucleus accumbens,it can regulate the discharge of glucose sensitive neurons and gastric motility,and this way maybe mediated by the orexin-A receptor signaling pathway.