Glucocorticoids interact with the basolateral amygdala β-adrenoceptor-cAMP/PKA system in influencing memory consolidation

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 3',5'-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 alpha(1)-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 alpha(1)-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.