School of Psychology, University of Sydney, Australia.
School of Psychology, University of Sydney, Australia.
Neurobiol Learn Mem. 2018 May;151:59-70. doi: 10.1016/j.nlm.2018.04.009. Epub 2018 Apr 9.
A critical barrier to recovery from alcohol addiction is relapse propensity. Alcohol cues can trigger relapse, and pharmacologically facilitating processes such as extinction, which decreases cue associations, may help prevent relapse. The noradrenergic system mediates extinction learning for alcohol; however, the neural locus of this effect is unknown. This study sought to determine whether the basolateral amygdala (BLA), a region critical for fear extinction, also mediates extinction of alcohol seeking. Hooded Wistar rats (N = 12-15 per experiment) were implanted with bilateral cannula targeting the BLA and trained to lever press for 10% ethanol during auditory or visual cues. Infusions of the β-receptor antagonist propranolol (2 µg/side) were administered prior to extinction (Experiment 1), and rats assessed for relapse-like behaviour two weeks later, thus allowing for spontaneous recovery. We expected intra-BLA propranolol to impair extinction learning; however, propranolol-treated rats exhibited reduced responding in the test of spontaneous recovery, suggesting enhanced extinction. We investigated this unexpected result by determining if propranolol treatment affected memory processes other than extinction. In a subsequent experiment, rats were infused with propranolol immediately after extinction to target consolidation of extinction (Experiment 2a), and assessed for spontaneous recovery. Propranolol was also infused after self-administration to target reconsolidation of the original learning (Experiment 2b). Propranolol treatment had no effect on consolidation of extinction learning, but impaired reconsolidation of self-administration. Propranolol administered prior to a self-administration session did not affect reinforced responding (Experiment 2c). Extinction and reconsolidation are opposing processes triggered by specific test conditions. We suggest our test conditions induced reconsolidation of self-administration memory by propranolol, rather than modulation of extinction. Thus, our data implicates intra-BLA noradrenergic β-receptors in reconsolidation of alcohol self-administration memory.
酒精成瘾康复的一个关键障碍是复发倾向。酒精线索会引发复发，而促进诸如消退等药理学过程，减少线索关联，可能有助于预防复发。去甲肾上腺素能系统介导酒精的消退学习；然而，这种效应的神经中枢位置尚不清楚。本研究旨在确定外侧杏仁核（BLA）是否也介导了酒精寻求的消退，BLA 是恐惧消退的关键区域。有头 Wistar 大鼠（每个实验 12-15 只）双侧植入了针对 BLA 的导管，并在听觉或视觉线索期间接受了 lever press 训练以获得 10%乙醇。在消退前（实验 1）给予β受体拮抗剂普萘洛尔（2μg/侧）输注，两周后评估大鼠的类似复发行为，从而允许自发恢复。我们预计 BLA 内的普萘洛尔会损害消退学习；然而，普萘洛尔处理的大鼠在自发恢复测试中表现出减少的反应，表明消退增强。我们通过确定普萘洛尔治疗是否会影响除消退以外的记忆过程来研究这个意外结果。在随后的实验中，大鼠在消退后立即给予普萘洛尔输注以靶向消退的巩固（实验 2a），并评估自发恢复。普萘洛尔也在自我给药后输注以靶向原始学习的再巩固（实验 2b）。普萘洛尔治疗对消退学习的巩固没有影响，但损害了自我给药的再巩固。在自我给药之前给予普萘洛尔治疗不会影响强化反应（实验 2c）。消退和再巩固是由特定测试条件引发的相反过程。我们认为我们的测试条件通过普萘洛尔诱导了自我给药记忆的再巩固，而不是调节消退。因此，我们的数据表明，BLA 内的去甲肾上腺素能β受体参与了酒精自我给药记忆的再巩固。
