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

Abstract

Infusion of a β‐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 β‐adrenoceptor–cAMP system in the BLA in modulating memory consolidation. Male, Sprague–Dawley rats received bilateral infusions of atenolol (a β‐adrenoceptor antagonist), prazosin (an α 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 α 1‐adrenoceptor activation and attenuated the dose–response effects of post‐training intra‐BLA infusions of clenbuterol (a β‐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 β‐adrenoceptor–cAMP cascade, at a locus between the membrane‐bound β‐adrenoceptor and the intracellular cAMP formation site.