Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala.
Previous findings indicate that administration of abeta-adrenoceptor antagonist systemically blocks glucocorticoid impairment of memory retrieval. Here, we report that beta-adrenoceptor activation in the hippocampus and the basolateral complex of the amygdala (BLA) is implicated in the impairing effects of glucocorticoids on memory retrieval. The specific glucocorticoid receptor (GR) agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362) (15 ng) infused into the hippocampus of male Sprague Dawley rats 60 min before water maze retention testing, 24 hr after training, impaired probe trial retention performance, as assessed by quadrant search time and initial latency to cross the platform location. Because we found previously that RU 28362 infused into the hippocampus does not affect water maze acquisition or immediate recall, the findings suggest that the GR agonist-induced retention impairment was attributable to a selective influence on long-term memory retrieval. Likewise, systemic injections of the beta1-adrenoceptor partial agonist xamoterol (3.0 or 10.0 mg/kg, s.c.) 60 min before the probe trial dose-dependently impaired retention performance. The beta-adrenoceptor antagonist propranolol (2.0 mg/kg) administered subcutaneously before retention testing did not affect retention performance alone, but blocked the memory retrieval impairment induced by concurrent intrahippocampal infusions of RU 28362. Pretest infusions of the beta1-adrenoceptor antagonist atenolol into either the hippocampus (1.25 microg in 0.5 microl) or the BLA (0.5 microg in 0.2 microl) also prevented the GR agonist-induced memory retrieval impairment. These findings suggest that glucocorticoids impair retrieval of long-term spatial memory by facilitating noradrenergic mechanisms in the hippocampus, and additionally, that norepinephrine-mediated BLA activity is critical in enabling hippocampal glucocorticoid effects on memory retrieval.
Roozendaal
Benno
B
Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, California 92697-3800, USA. broozend@uci.edu
Hahn
Emily L
EL
Nathan
Sheila V
SV
de Quervain
Dominique J-F
DJ
McGaugh
James L
JL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology / Q000502:physiology*; D004644:Emotions; D004924:Escape Reaction / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D011939:Mental Recall / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology; D017307:Xamoterol / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000732:Androstanols; D006727:Hormone Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D011965:Receptors, Glucocorticoid; D001262:Atenolol; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D017307:Xamoterol; D011433:Propranolol; D003345:Corticosterone