Roozendaal Benno, Quirarte Gina L, McGaugh James L
Center for the Neurobiology of Learning and Memory and Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-3800, USA.
Eur J Neurosci. 2002 Feb;15(3):553-60. doi: 10.1046/j.0953-816x.2001.01876.x.
Infusion of a beta-adrenoceptor antagonist into the basolateral nucleus of the amygdala (BLA) blocks memory enhancement induced by systemic or intra-BLA administration of a glucocorticoid receptor (GR) agonist. As there is evidence that glucocorticoids interact with the noradrenergic signalling pathway in activating adenosine 3prime prime or minute,5prime prime or minute-cyclic monophosphate (cAMP), the present experiments examined whether glucocorticoids influence the beta-adrenoceptor--cAMP system in the BLA in modulating memory consolidation. Male, Sprague--Dawley rats received bilateral infusions of atenolol (a beta-adrenoceptor antagonist), prazosin (an alpha1-adrenoceptor antagonist) or Rp-cAMPS (a protein kinase A inhibitor) into the BLA 10 min before inhibitory avoidance training and immediate post-training intra-BLA infusions of the GR agonist, RU 28362. Atenolol and Rp-cAMPS, but not prazosin, blocked 48-h retention enhancement induced by RU 28362. A second series of experiments investigated whether a GR antagonist alters the effect of noradrenergic activation in the BLA on memory consolidation. Bilateral intra-BLA infusions of the GR antagonist, RU 38486, administered 10 min before inhibitory avoidance training completely blocked retention enhancement induced by alpha1-adrenoceptor activation and attenuated the dose--response effects of post-training intra-BLA infusions of clenbuterol (a beta-adrenoceptor agonist). However, the GR antagonist did not alter retention enhancement induced by post-training intra-BLA infusions of 8-Br-cAMP (a synthetic cAMP analogue). These findings suggest that glucocorticoids influence the efficacy of noradrenergic stimulation in the BLA on memory consolidation via an interaction with the beta-adrenoceptor--cAMP cascade, at a locus between the membrane-bound beta-adrenoceptor and the intracellular cAMP formation site.
将β-肾上腺素能受体拮抗剂注入杏仁核基底外侧核（BLA）可阻断全身或BLA内注射糖皮质激素受体（GR）激动剂所诱导的记忆增强。由于有证据表明糖皮质激素在激活腺苷3′,5′-环磷酸（cAMP）时与去甲肾上腺素能信号通路相互作用，因此本实验研究了糖皮质激素是否通过影响BLA中的β-肾上腺素能受体-cAMP系统来调节记忆巩固。雄性Sprague-Dawley大鼠在抑制性回避训练前10分钟接受双侧BLA注射阿替洛尔（一种β-肾上腺素能受体拮抗剂）、哌唑嗪（一种α1-肾上腺素能受体拮抗剂）或Rp-cAMPS（一种蛋白激酶A抑制剂），并在训练后立即进行BLA内注射GR激动剂RU 28362。阿替洛尔和Rp-cAMPS可阻断RU 28362诱导的48小时记忆保持增强，而哌唑嗪则无此作用。第二系列实验研究了GR拮抗剂是否会改变BLA中去甲肾上腺素能激活对记忆巩固的影响。在抑制性回避训练前10分钟进行双侧BLA内注射GR拮抗剂RU 38486，可完全阻断α1-肾上腺素能受体激活所诱导的记忆保持增强，并减弱训练后BLA内注射克仑特罗（一种β-肾上腺素能受体激动剂）的剂量-反应效应。然而，GR拮抗剂并未改变训练后BLA内注射8-Br-cAMP（一种合成cAMP类似物）所诱导的记忆保持增强。这些发现表明，糖皮质激素通过与β-肾上腺素能受体-cAMP级联相互作用，在膜结合β-肾上腺素能受体和细胞内cAMP形成位点之间的某个位置，影响BLA中去甲肾上腺素能刺激对记忆巩固的功效。
