Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC 88049-900, Brazil.
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC 88049-900, Brazil; Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.
Neuropharmacology. 2018 Jun;135:253-267. doi: 10.1016/j.neuropharm.2018.02.029. Epub 2018 Feb 27.
The main κ opioid receptors (κORs) subtypes already described (κORs and κORs) are expressed in brain regions involved in aversive memory consolidation, including the dorsal hippocampus (DH). However, the role of DH κORs in consolidation of aversive memories with varied intensity and specificity is still uncertain. The present study aimed to investigate this question using pharmacological agents in rats subjected to a weak, moderate or strong contextual aversive conditioning (CAC) protocol. Antagonizing DH κORs with nor-binaltorphimine (nor-BNI), immediately after, but not 6 h later, a moderate CAC leads to intensified freezing behavior in the re-exposure to the paired context. Thus, indicating that DH κORs have an inhibitory role in the consolidation of an aversive memory. Increased DH κORs expression 1 h and 3 h after the moderate CAC was also observed. This up-regulation was absent in animals only exposed to the shock or to the context, indicating that this phenomenon requires a shock-context pairing to occur. Intra-DH nor-BNI infusion induced no changes following a weak CAC, but it was able to potentiate the expression of freezing behavior in novel and unpaired context after a strong CAC, indicating that DH κORs also modulate the consolidation of a more intense and generalized memory. Moreover, infusing the κORs agonist GR 89696, but not the κORs agonist U-69593, into the DH reduced the conditioned freezing expression. Nor-BNI pretreatment in a sub-effective dose prevented the κORs agonist effects. Altogether, the present findings provide convergent evidence that κORs activation negatively modulates contextual aversive memory consolidation in rat dorsal hippocampus.
已经描述的主要 κ 阿片受体（κORs）亚型（κORs 和 κORs）在参与厌恶记忆巩固的大脑区域中表达，包括背侧海马体（DH）。然而，DH κORs 在巩固具有不同强度和特异性的厌恶记忆中的作用仍然不确定。本研究旨在使用药理学制剂在经历弱、中或强情境性厌恶条件作用（CAC）方案的大鼠中研究这个问题。在中等 CAC 后但不在 6 小时后立即用 nor-binaltorphimine（nor-BNI）拮抗 DH κORs 导致在重新暴露于配对环境时冻结行为加剧。因此，表明 DH κORs 在厌恶记忆的巩固中具有抑制作用。还观察到在中等 CAC 后 1 小时和 3 小时 DH κORs 表达增加。在仅暴露于电击或环境的动物中未观察到这种上调，表明这种现象需要发生电击-环境配对。在弱 CAC 后，DH 内 nor-BNI 输注不会引起变化，但在强 CAC 后，它能够增强在新的和未配对的环境中的冻结行为表达，表明 DH κORs 也调节更强烈和更广泛的记忆的巩固。此外，将 κORs 激动剂 GR 89696 而不是 κORs 激动剂 U-69593 注入 DH 减少了条件性冻结表达。在亚有效剂量下进行 nor-BNI 预处理可防止 κORs 激动剂的作用。总之，这些发现提供了一致的证据，表明 κORs 激活负调节大鼠背侧海马体的情境性厌恶记忆巩固。
