Kertes Erika, Péczely László, Ollmann Tamás, László Kristóf, Berta Beáta, Kállai Veronika, Zagorácz Olga, Kovács Anita, Szabó Ádám, Karádi Zoltán, Lénárd László
Institute of Physiology, University of Pécs, Medical School, Pécs, Hungary.
Centre for Neuroscience, University of Pécs, Pécs, Hungary.
Int J Neuropsychopharmacol. 2024 Dec 28;28(1). doi: 10.1093/ijnp/pyaf002.
The tachykinin substance P (SP) facilitates learning and memory processes after its central administration. Activation of its different receptive sites, neurokinin-1 receptors (NK1Rs), as well as NK2Rs and NK3Rs, was shown to influence learning and memory. The basal ganglia have been confirmed to play an important role in the control of memory processes and spatial learning mechanisms, and as part of the basal ganglia, the globus pallidus (GP) may also be involved in this regulation. SP-immunoreactive fibers and terminals, as well as NK1Rs and NK3Rs, were shown to be present in the GP.
The present study aimed to examine whether the SP administered into the GP can influence spatial memory consolidation in the Morris water maze (MWM). Therefore, male Wistar rats received a post-trial microinjection of 0.4 µLf 10 ng SP, 100 ng SP, or vehicle solution. The possible involvement of pallidal NK1Rs and NK3Rs in the SP effects was also studied by applying WIN51708 for NK1R antagonism and SR142801 as a selective NK3R antagonist.
Our results showed that the lower dose of SP significantly decreased escape latency on the second day compared to control animals, while the higher dose was ineffective. Prior treatment with the NK1R antagonist WIN51708 could not block, while the NK3R antagonist SR142801 inhibited the effects of SP on memory consolidation in the MWM.
Our results are the first to demonstrate that SP improves consolidation of spatial memory in the GP, and this effect is mediated through NK3Rs but not NK1Rs.
速激肽P物质(SP)经中枢给药后可促进学习和记忆过程。研究表明,其不同受体位点(神经激肽-1受体(NK1R)以及NK2R和NK3R)的激活会影响学习和记忆。基底神经节已被证实对记忆过程和空间学习机制的控制起着重要作用,作为基底神经节的一部分,苍白球(GP)可能也参与了这一调节过程。研究显示,GP中存在SP免疫反应性纤维和终末,以及NK1R和NK3R。
本研究旨在探讨向GP注射SP是否会影响Morris水迷宫(MWM)中的空间记忆巩固。因此,雄性Wistar大鼠在试验后接受0.4μL 10 ng SP、100 ng SP或溶媒溶液的微量注射。还通过应用WIN51708拮抗NK1R以及使用SR142801作为选择性NK3R拮抗剂,研究了苍白球NK1R和NK3R在SP效应中的可能作用。
我们的结果显示,与对照动物相比,较低剂量的SP在第二天显著缩短了逃避潜伏期,而较高剂量则无效。NK1R拮抗剂WIN51708预处理不能阻断SP的作用,而NK3R拮抗剂SR142801抑制了SP对MWM中记忆巩固的影响。
我们的结果首次表明,SP可改善GP中的空间记忆巩固,且这种效应是通过NK3R而非NK1R介导的。