Glucocorticoid enhancement of memory consolidation in the rat is blocked by muscarinic receptor antagonism in the basolateral amygdala.
Glucocorticoid-induced memory enhancement is known to depend on beta-adrenoceptor activation in the basolateral amygdala (BLA). Additionally, inactivation of muscarinic cholinergic receptors in the rat amygdala blocks memory enhancement induced by concurrent beta-adrenergic activation. Together, these findings suggest that glucocorticoid-induced modulation of memory consolidation requires cholinergic as well as adrenergic activation in the BLA. Two experiments investigated this issue. The first experiment examined whether blockade of muscarinic cholinergic receptors in the BLA with atropine alters the memory-enhancing effects of the systemically administered glucocorticoid dexamethasone. Dexamethasone (0.3, 1.0 or 3.0 mg/kg, s.c.) administered to rats immediately after inhibitory avoidance training produced dose-dependent enhancement of 48-h retention. Concurrent bilateral infusions of the muscarinic cholinergic antagonist atropine (0.5 microg in 0.2 microL per side) into the BLA blocked the memory enhancement. The second experiment investigated whether the BLA is a locus of interaction between glucocorticoid and muscarinic activation. The specific glucocorticoid receptor (GR or type II) agonist RU 28362 (1.0, 3.0 or 10 ng) was infused into the BLA either alone or together with atropine immediately after training. The GR agonist produced dose-dependent memory enhancement and atropine blocked the memory enhancement. These findings indicate that muscarinic cholinergic activation within the BLA is critical for enabling glucocorticoid enhancement of memory consolidation and that enhancement of memory induced by GR activation in the BLA requires cholinergic activation within the BLA.
Power
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AE
Center for the Neurobiology of Learning and Memory, and Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-3800, USA. apower@uci.edu
Roozendaal
B
B
McGaugh
J L
JL
D000109:Acetylcholine / Q000378:metabolism; D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
D000732:Androstanols; D005938:Glucocorticoids; D018727:Muscarinic Antagonists; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D001285:Atropine; D003907:Dexamethasone; D000109:Acetylcholine