The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: dependence on the basolateral amygdala.
Previous studies have indicated that stress-activated glucocorticoid hormones induce temporary memory retrieval impairment. The present study examined whether adrenal steroid receptors in the hippocampus mediate such glucocorticoid effects on spatial memory retrieval. The specific glucocorticoid receptor (GR) agonist 11beta, 17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362; 5 or 15 ng) infused into the hippocampus of male Sprague-Dawley rats 60 min before water-maze retention testing, 24 h after training, dose-dependently impaired probe-trial retention performance, as assessed both by time spent in the training quadrant and initial latency to cross the platform location. The GR agonist did not affect circulating corticosterone levels immediately after the probe trial, indicating that RU 28362 infusions did not influence retention by altering glucocorticoid feedback mechanisms. As infusions of the GR agonist into the hippocampus 60 min before training did not influence water-maze acquisition or immediate recall, the findings indicated that the GR agonist-induced retention impairment was induced selectively by an influence on information retrieval. In contrast, pretest infusions of the GR agonist administered into the basolateral complex of the amygdala (BLA; 2 or 6 ng) did not alter retention performance in the water maze. However, N-methyl-d-aspartate-induced lesions of the BLA, made 1 week before training, blocked the memory retrieval impairment induced by intrahippocampal infusions of RU 28362 given 60 min before the retention test. These findings indicate that the effects of glucocorticoids on retrieval of long-term spatial memory depend on the hippocampus and, additionally, that neuronal input from the BLA is critical in enabling hippocampal glucocorticoid effects on memory retrieval.
Roozendaal
Benno
B
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
Griffith
Qyana K
QK
Buranday
Jason
J
De Quervain
Dominique J-F
DJ
McGaugh
James L
JL
D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism*; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D000732:Androstanols; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D016202:N-Methylaspartate; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one