Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
Neurobiol Learn Mem. 2023 Nov;205:107829. doi: 10.1016/j.nlm.2023.107829. Epub 2023 Sep 19.
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.
糖皮质激素给药，无论是在恐惧记忆再激活之前还是之后，都会损害随后的恐惧记忆表达，但其中的机制尚不清楚。本研究探讨了外侧杏仁核（BLA）β-肾上腺素受体在 BLA 内皮质酮注射对大鼠恐惧记忆的影响中的作用。雄性 Wistar 大鼠双侧植入 BLA 套管。使用抑制性回避任务（3 秒 1 mA 足底电击）对大鼠进行训练和测试。在训练后 48 小时，将皮质酮（CORT，5、10 或 20ng/0.5μl/侧）和β2-肾上腺素受体激动剂克仑特罗（CLEN，10 或 20ng/0.5μl/侧）或β-肾上腺素受体拮抗剂普萘洛尔（PROP，250 或 500ng/0.5μl/侧）注入 BLA，然后在记忆再激活（检索，测试 1）之前或之后立即进行。我们在测试 1 后 2（测试 2）、5（测试 3）、7（测试 4）和 9（测试 5）天进行了随后的测试。结果表明，测试 1 前的 CORT 注射破坏了记忆检索，并降低了测试 2-5 中的恐惧表达，这可能是由于增强的消退或受损的再巩固。测试 1 后 CORT 注射也损害了再巩固，并降低了测试 2-5 中的恐惧表达。CLEN 预防，但 PROP 加剧，CORT 对恐惧表达的影响。提醒冲击并未恢复 CORT 处理动物的恐惧记忆，表明受影响的是再巩固，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再巩固和表达。理解应激的神经生物学以及糖皮质激素对恐惧记忆的影响可能为 PTSD 等应激和创伤后障碍的新治疗方法提供思路。
