Orexin-A Affects Gastric Distention Sensitive Neurons In The Hippocampus And Gastric Motility And Regulation By The Perifornical Area In Rats

Objective: To elucidate the effects and the potential regulation mechanisms of orexin-A and the perofornical area(Pe F)-hippocampus(Hi) neural pathways on electrical activity of gastric distension(GD)sensitive neurons in hippocampus and gastric motility.Methods: This study consisted of 266 adult male Wistar rats weighing 250–300 g. Methods of a retrograde tracing combined with immunohistochemistry staining, extracellular discharges of single unit neuron recording, nuclei microinjection of orexin-A and orexin-A antagonist SB334867, and electrical stimulation of Pe F were performed to illustrate the effects of orexin-A in Hi on gastric distension(GD)sensitive neurons as well as gastric motility and the regulation by the Pe F.Results: Orexin-A/ fluorogold(FG) dual labelled neurons were detected in the Pe F after injection of FG into Hi for 7 days, which inferred that some orexin-A immunoreactive neuronal projections from Pe F to Hi. The results of gastric motility study illustrated that orexin-A administered to the Hi dose-dependently increased the amplitude and frequency of the gastric motility(P<0.05–0.01). Pretreatment with SB-334867 completely blocked the effects of orexin-A. Electrical stimulate Pe F also increased the amplitude and frequency of the gastric motility significantly(p<0.01). However, pretreatment with SB-334867 partly attenuated the effects of stimulation in Pe F(p< 0.01).90 rats were used to observe the effects of orexin-A and SB-334867-A on discharge activity of GD-responsive neurons. 63 were identified as GD-E neurons, while 56 neurons were identified as GD-I neurons. Upon microinjection of orexin-A into the Hi 42 of 63(42/63, 66.7%) GD-E neurons were activated(P < 0.01) and 13(13/63, 20.6%) GD-E neurons were inhibited. Out of the 56 GD-I neurons,35 neurons excited by orexin-A(P < 0.01) while 14 neurons were inhibited(P<0.01). The effects induced by orexin-A were abolished with pre-administration of SB-334867 into the Hi. Electrical stimulation to neurons was performed in the Pe F of 75 rats. 80 GD-E neurons and 62 GD-I neurons were identified. 57 of 80(57/80, 71.25%) GD-E neurons were excited by orexin-A. Out of these 57 orexin-A exciting GD-E neurons, 43(43/57, 75.43%) were further excited by electrical stimulation of the Pe F with firing rates that markedly increased(P < 0.01) and 8(8/57, 14%) neurons were inhibited(P<0.01). For GD-I neurons, 41 of 62(41/62, 66.13%) were excited by an injection of orexin-A.28 of the 41(28/41, 68.29%) orexin-A exciting GD-I neurons were also excited by electrical stimulation of the Pe F(P < 0.01), 7(7/41, 17.07%) neurons were inhibited(P<0.01). Meanwhile, responses induced by electrical stimulation of the Pe F diminished upon pre-treatment with the orexin-A receptor antagonist SB-334867 in the Hi, this was seen in both orexin-A responsive GD-E and GD-I neurons(p < 0.05).Conclusions: There exist a direct pathway of orexin-A from the perifornical area to the hippocampus. The Pe F-Hi neural pathways and orexin-A can regulate gastric motility and electrical activity of gastric distension(GD)sensitive neurons in Hi. Orexin-A administration to the Hi excited the GD-neurons and increased the amplitude and frequency of gastric motility in a dose-dependent manner.