Abstract

Glucocorticoid administration, before or after fear memory reactivation, impairs subsequent fear memory expression, but the underlying mechanisms are not well understood. The present study examined the role of basolateral amygdala (BLA) β-adrenoceptors in the effects of intra-BLA corticosterone injection on fear memory in rats. Bilateral cannulae were implanted in the BLA of Wistar male rats. The rats were trained and tested using an inhibitory avoidance task (1 mA footshock for 3 s). Forty-eight hours after training, corticosterone (CORT, 5, 10, or 20 ng/0.5 µl/side) and the β2-adrenoceptor agonist clenbuterol (CLEN, 10 or 20 ng/0.5 µl/side) or the β-adrenoceptor antagonist propranolol (PROP, 250 or 500 ng/0.5 µl/side) were injected into the BLA before or right after memory reactivation (retrieval, Test 1). We performed subsequent tests 2 (Test 2), 5 (Test 3), 7 (Test 4), and 9 (Test 5) days after Test 1. The results demonstrated that CORT injection before Test 1 disrupted memory retrieval and reduced fear expression in Tests 2–5, possibly due to enhanced extinction or impaired reconsolidation. CORT injection after Test 1 also impaired reconsolidation and reduced fear expression in Tests 2–5. CLEN prevented, but PROP exacerbated, the effects of CORT on fear expression. The reminder shock did not recover fear memory in CORT-treated animals, suggesting that reconsolidation, not extinction, was affected. These results indicate that glucocorticoids and β-adrenoceptors in the BLA jointly modulate fear memory reconsolidation and expression. Comprehending the neurobiology of stress and the impact of glucocorticoids on fear memory may lead to new treatments for stress and trauma-induced disorders such as PTSD.

中文翻译：

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记忆重新激活前后向基底外侧杏仁核注射皮质酮会损害大鼠随后的恐惧记忆表达：糖皮质激素和β-肾上腺素受体的相互作用

摘要

在恐惧记忆重新激活之前或之后给予糖皮质激素会损害随后的恐惧记忆表达，但其潜在机制尚不清楚。本研究探讨了基底外侧杏仁核 (BLA) β-肾上腺素受体在 BLA 内注射皮质酮对大鼠恐惧记忆的影响中的作用。将双侧插管植入 Wistar 雄性大鼠的 BLA 中。使用抑制性回避任务（1 mA 足部电击 3 秒）对大鼠进行训练和测试。训练后 48 小时，皮质酮（CORT，5、10 或 20 ng/0.5 µl/侧）和 β2-肾上腺素受体激动剂克仑特罗（CLEN，10 或 20 ng/0.5 µl/侧）或 β-肾上腺素受体拮抗剂在记忆重新激活之前或之后立即将普萘洛尔（PROP，250 或 500 ng/0.5 µl/侧）注射到 BLA 中（检索，测试 1）。我们在测试 1 后的第 2 天（测试 2）、第 5 天（测试 3）、第 7 天（测试 4）和第 9 天（测试 5）进行了后续测试。结果表明，在测试 1 之前注射 CORT 会扰乱记忆检索并减少恐惧表达。测试 2-5，可能是由于消退增强或再巩固受损。测试 1 后注射 CORT 也会损害测试 2-5 中的再巩固并减少恐惧表达。CLEN 阻止了 CORT 对恐惧表达的影响，但 PROP 加剧了这种影响。提醒电击并没有恢复 CORT 治疗动物的恐惧记忆，这表明受影响的是重新巩固，而不是消退。这些结果表明，BLA 中的糖皮质激素和 β-肾上腺素受体共同调节恐惧记忆的重新巩固和表达。了解压力的神经生物学以及糖皮质激素对恐惧记忆的影响可能会带来针对压力和创伤引起的疾病（如创伤后应激障碍）的新疗法。