Hasenöhrl R U, Jentjens O, De Souza Silva M A, Tomaz C, Huston J P
Institute of Physiological Psychology and Center for Biological and Medical Research, University of Düsseldorf, Germany.
Eur J Pharmacol. 1998 Aug 7;354(2-3):123-33. doi: 10.1016/s0014-2999(98)00441-5.
There is evidence that the neurokinin substance P plays a role in neural mechanisms governing learning and reinforcement. Reinforcing and memory-promoting effects of substance P were found after it was injected into several parts of the brain and intraperitoneally. With regard to the close link between anxiety and memory processes for negative reinforcement learning, the aim of the present study was to gauge the effect of substance P on anxiety-related behaviors in the rat elevated plus-maze and social interaction test. Substance P was tested at injection sites where the neurokinin has been shown to promote learning and to serve as a reinforcer, namely in the periphery (after i.p. administration) and after injection into the nucleus basalis magnocellularis region. When administered i.p., substance P had a biphasic dose-response effect on behavior in the plus-maze with an anxiolytic-like action at 50 microg/kg and an anxiogenic-like one at 500 microg/kg. After unilateral microinjection into the nucleus basalis magnocellularis region, substance P (1 ng) was found to exert anxiolytic-like effects, because substance P-treated rats spent more time on the open arms of the plus-maze and showed an increase in time spent in social interaction. Furthermore, the anxiolytic effects of intrabasalis substance P were sequence-specific since injection of a compound with the inverse amino acid sequence of substance P (0.1 to 100 ng) did not influence anxiety parameters. These results show that substance P has anxiolytic-like properties in addition to its known promnestic and reinforcing effects, supporting the hypothesis of a close relationship between anxiety, memory and reinforcement processes.
有证据表明，神经激肽P物质在调控学习与强化的神经机制中发挥作用。将P物质注入大脑的几个部位及腹腔后，发现了其具有强化和促进记忆的作用。鉴于焦虑与负强化学习的记忆过程之间存在紧密联系，本研究的目的是评估P物质对大鼠高架十字迷宫和社交互动测试中焦虑相关行为的影响。在已证明神经激肽可促进学习并作为强化物的注射部位对P物质进行测试，即在外周（腹腔注射后）以及注入基底大细胞核区域后进行测试。腹腔注射时，P物质对十字迷宫中的行为具有双相剂量反应效应，50微克/千克时具有抗焦虑样作用，500微克/千克时具有致焦虑样作用。单侧微量注射到基底大细胞核区域后，发现P物质（1纳克）发挥抗焦虑样作用，因为经P物质处理的大鼠在十字迷宫开放臂上花费更多时间，且社交互动时间增加。此外，基底内注射P物质的抗焦虑作用具有序列特异性，因为注射具有与P物质相反氨基酸序列的化合物（0.1至100纳克）不会影响焦虑参数。这些结果表明，P物质除了具有已知的促进记忆和强化作用外，还具有抗焦虑样特性，支持了焦虑、记忆和强化过程之间存在密切关系的假设。
