Orexin-A is an endogenous peptide with receptors throughout the brain. According to some recent research, learning and memory are affected by the central administration of orexin; however, no study so far has investigated the long-term inhibition of the orexinergic system. The present study has evaluated the effect of pretraining administration of orexin 1 receptor (OXR1) antagonist, SB-334867, on the acquisition of memory. The Morris water maze (MWM) task was used for training and trial purposes in all groups. Memory performance was analyzed by measuring escape latency, traveled distance, and time spent in the target quadrant. Moreover, the effect of SB-334867 on phospholipase Cβ3 (PLCβ3) levels in the CA1 region of hippocampus slices was examined. Hippocampus slices were prepared using an immunohistochemistry (IHC) approach. SB-334867 (20 mg/kg) increased escape latency in SB-treated rats compared to SB-vehicle group ( < 0.01). SB-treated rats spent less time in the target quadrant compared to the SB-vehicle group ( < 0.001). Distance traveled in the target quadrant was significantly more in SB-treated rats compared to the SB-vehicle group ( < 0.001). Furthermore, SB-334867 decreased PLCβ3 levels in the CA1 of the hippocampus ( < 0.01 and < 0.05, respectively). Put together, our results suggest that the long-term inhibition of OXR1 plays a prominent role in spatial learning and memory, probably by attenuating PLCβ3 in CA1 neurons.

中文翻译：

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Morris 水迷宫评估海马中的磷脂酶 Cβ3 可能通过长期阻断食欲素 1 受体介导记忆损伤

食欲素-A 是一种内源性肽，其受体遍布整个大脑。根据最近的一些研究，学习和记忆会受到中枢食欲素的影响。然而，迄今为止还没有研究调查食欲素系统的长期抑制作用。本研究评估了训练前施用食欲素 1 受体 (OXR1) 拮抗剂 SB-334867 对记忆获得的影响。莫里斯水迷宫（MWM）任务用于所有组的训练和试验目的。通过测量逃避潜伏期、移动距离和在目标象限中花费的时间来分析记忆性能。此外，还检查了 SB-334867 对海马切片 CA1 区磷脂酶 Cβ3 (PLCβ3) 水平的影响。使用免疫组织化学 (IHC) 方法制备海马切片。与 SB 媒介物组相比，SB-334867 (20 mg/kg) 增加了 SB 治疗大鼠的逃避潜伏期 ( < 0.01)。与 SB 载体组相比，SB 治疗组大鼠在目标象限中花费的时间更少 ( < 0.001)。与 SB 载体组相比，SB 治疗组大鼠在目标象限中移动的距离显着更长 ( < 0.001)。此外，SB-334867 降低了海马 CA1 区的 PLCβ3 水平（分别 < 0.01 和 < 0.05）。综上所述，我们的结果表明，长期抑制 OXR1 在空间学习和记忆中发挥着重要作用，可能是通过减弱 CA1 神经元中的 PLCβ3 来实现的。