Roozendaal Benno, McReynolds Jayme R, McGaugh James L
Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, California 92697-3800, USA.
J Neurosci. 2004 Feb 11;24(6):1385-92. doi: 10.1523/JNEUROSCI.4664-03.2004.
Previous findings indicate that the basolateral complex of the amygdala (BLA) interacts with other brain regions in regulating stress hormone effects on memory functions. Lesions of the BLA or infusions of a beta-adrenoceptor antagonist into the BLA block glucocorticoid effects on both memory consolidation and retrieval when administered either systemically or directly into the hippocampus. The present experiments examined BLA and beta-adrenoceptor involvement in regulating glucocorticoid effects on spatial working memory, a task that depends on the medial prefrontal cortex (mPFC). Male Sprague Dawley rats with bilateral sham- or NMDA-induced lesions of the BLA received either corticosterone (1.0 or 3.0 mg/kg, i.p.) systemically or the specific glucocorticoid receptor agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362; 3.0 or 10.0 ng in 0.5 microl) into the mPFC shortly before testing on a delayed alternation task in a T-maze. Both glucocorticoid treatments induced comparable impairments in working memory performance in sham-lesioned controls. Although lesions of the BLA alone did not affect working memory, BLA lesions blocked the impairment induced by either corticosterone or RU 28362. Likewise, systemic injections of the centrally acting beta-adrenoceptor antagonist propranolol (2.0 mg/kg, i.p.) given before testing prevented corticosterone-induced working memory impairment. These findings indicate that BLA activity is essential for enabling glucocorticoid effects in the mPFC on working memory and suggest that stress hormone-induced modulation of working memory involves noradrenergic activation.
先前的研究结果表明，杏仁核基底外侧复合体（BLA）在调节应激激素对记忆功能的影响时会与其他脑区相互作用。当全身给药或直接注入海马体时，BLA损伤或向BLA注入β-肾上腺素能受体拮抗剂会阻断糖皮质激素对记忆巩固和提取的影响。本实验研究了BLA和β-肾上腺素能受体在调节糖皮质激素对空间工作记忆的影响中的作用，空间工作记忆任务依赖于内侧前额叶皮质（mPFC）。对双侧进行假手术或NMDA诱导的BLA损伤的雄性Sprague Dawley大鼠，在T迷宫中进行延迟交替任务测试前不久，全身给予皮质酮（1.0或3.0mg/kg，腹腔注射），或向mPFC注入特异性糖皮质激素受体激动剂11β,17β-二羟基-6,21-二甲基-17α-孕甾-4,6-二烯-20-炔-3-酮（RU 28362；0.5微升中含3.0或10.0纳克）。两种糖皮质激素处理在假损伤对照组的工作记忆表现中均诱导了类似的损伤。虽然单独的BLA损伤不影响工作记忆，但BLA损伤阻断了皮质酮或RU 28362诱导的损伤。同样，在测试前全身注射中枢作用的β-肾上腺素能受体拮抗剂普萘洛尔（2.0mg/kg，腹腔注射）可预防皮质酮诱导的工作记忆损伤。这些发现表明，BLA活性对于使糖皮质激素在mPFC中对工作记忆产生作用至关重要，并表明应激激素诱导的工作记忆调节涉及去甲肾上腺素能激活。
