回避条件刺激增强记忆巩固：D3 受体的调制。

Enhancement of memory consolidation by an avoidance conditioned stimulus: Modulation by the D3 receptor.

机构信息

Department of Psychology and Collaborative Program in Neuroscience, University of Guelph, Guelph, ON, Canada.

出版信息

Neuropharmacology. 2023 Sep 1;235:109572. doi: 10.1016/j.neuropharm.2023.109572. Epub 2023 May 4.

DOI:10.1016/j.neuropharm.2023.109572

Abstract

Conditioned stimuli (CS) paired with foot-shock can enhance memory consolidation. Because the dopamine D3 receptor (D3R) has been implicated in mediating various responses to CSs, the current study explored its potential role in modulation of memory consolidation by an avoidance CS. Male Sprague-Dawley rats trained to avoid foot-shocks in a two-way signalled active avoidance task (8 sessions, 30 trials per session, 0.8 mA foot-shock) were pre-treated with the D3R antagonist NGB-2904 (Vehicle, 0.1 or 5 mg/kg) and exposed to the CS immediately after the sample phase of an object recognition memory task. Discrimination ratios were assessed 72 h later. Immediate, but not delayed (6 h), post-sample exposure to the CS enhanced object recognition memory and this effect was blocked by NGB-2904. Control experiments with the beta-noradrenergic receptor antagonist propranolol (10 or 20 mg/kg) and D2R antagonist pimozide (0.2 or 0.6 mg/kg) indicated that NGB-2904 targeted post-training memory consolidation. Exploring the pharmacological selectivity of the NGB-2904 effect, it was found that: 1) 5 mg/kg NGB-2904 blocked conditioned memory modulation produced by post-sample exposure to a "weak" CS (one day of avoidance training) and concurrent stimulation of catecholamine activity by 10 mg/kg bupropion; and 2) post-sample exposure to a "weak" CS and concurrent administration of the D3R agonist 7-OH-DPAT (1 mg/kg) enhanced consolidation of object memory. Finally, because 5 mg/kg NGB-2904 had no effect on modulation by avoidance training in the presence of foot-shocks, the findings herein support the hypothesis that the D3R plays an important role in modulation of memory consolidation by CSs.

摘要

条件刺激 (CS) 与足部电击相结合可以增强记忆巩固。由于多巴胺 D3 受体 (D3R) 参与介导对 CS 的各种反应，因此当前研究探讨了其在回避 CS 调节记忆巩固中的潜在作用。在双向信号主动回避任务（8 个疗程，每个疗程 30 次试验，0.8 mA 足部电击）中接受足部电击回避训练的雄性 Sprague-Dawley 大鼠，预先接受 D3R 拮抗剂 NGB-2904（载体、0.1 或 5 mg/kg）处理，并在物体识别记忆任务的样本阶段后立即暴露于 CS。72 小时后评估辨别率。立即，但不延迟（6 小时），样本后暴露于 CS 增强了物体识别记忆，而这种作用被 NGB-2904 阻断。使用β-去甲肾上腺素能受体拮抗剂普萘洛尔（10 或 20 mg/kg）和 D2R 拮抗剂匹莫齐特（0.2 或 0.6 mg/kg）的对照实验表明，NGB-2904 针对的是训练后记忆巩固。探索 NGB-2904 作用的药理学选择性，发现：1）5 mg/kg NGB-2904 阻断了样本后暴露于“弱” CS（一天回避训练）和同时刺激儿茶酚胺活性（10 mg/kg 安非他酮）产生的条件记忆调节；2）样本后暴露于“弱” CS 和同时给予 D3R 激动剂 7-OH-DPAT（1 mg/kg）增强了物体记忆的巩固。最后，因为 5 mg/kg NGB-2904 对存在足部电击时的回避训练的调节没有影响，因此，这些发现支持了这样的假设，即 D3R 在 CS 调节记忆巩固中发挥重要作用。