title: Glucocorticoids interact with the basolateral amygdala beta-adrenoceptor--cAMP/cAMP/PKA system in influencing memory consolidation.
abstract: 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.
authors.affiliation: Center for the Neurobiology of Learning and Memory and Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-3800, USA. broozend@uci.edu
authors.forename: Benno
authors.initials: B
authors.lastname: Roozendaal
authors.forename: Gina L
authors.initials: GL
authors.lastname: Quirarte
authors.forename: James L
authors.initials: JL
authors.lastname: McGaugh
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D011965:Receptors, Glucocorticoid; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases