Document Detail


Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory.
MedLine Citation:
PMID:  22331883     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is extensive evidence that glucocorticoid hormones impair the retrieval of memory of emotionally arousing experiences. Although it is known that glucocorticoid effects on memory retrieval impairment depend on rapid interactions with arousal-induced noradrenergic activity, the exact mechanism underlying this presumably nongenomically mediated glucocorticoid action remains to be elucidated. Here, we show that the hippocampal endocannabinoid system, a rapidly activated retrograde messenger system, is involved in mediating glucocorticoid effects on retrieval of contextual fear memory. Systemic administration of corticosterone (0.3-3 mg/kg) to male Sprague-Dawley rats 1 h before retention testing impaired the retrieval of contextual fear memory without impairing the retrieval of auditory fear memory or directly affecting the expression of freezing behavior. Importantly, a blockade of hippocampal CB1 receptors with AM251 prevented the impairing effect of corticosterone on retrieval of contextual fear memory, whereas the same impairing dose of corticosterone increased hippocampal levels of the endocannabinoid 2-arachidonoylglycerol. We also found that antagonism of hippocampal β-adrenoceptor activity with local infusions of propranolol blocked the memory retrieval impairment induced by the CB receptor agonist WIN55,212-2. Thus, these findings strongly suggest that the endocannabinoid system plays an intermediary role in regulating rapid glucocorticoid effects on noradrenergic activity in impairing memory retrieval of emotionally arousing experiences.
Authors:
Piray Atsak; Daniela Hauer; Patrizia Campolongo; Gustav Schelling; James L McGaugh; Benno Roozendaal
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-02-13
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-29     Completed Date:  2012-05-08     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3504-9     Citation Subset:  IM    
Affiliation:
Department of Neuroscience, Section Anatomy, University Medical Center Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands. pirayy@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Acoustic Stimulation
Adrenergic beta-Antagonists / pharmacology
Animals
Arachidonic Acids / physiology*
Arousal / physiology
Benzoxazines / pharmacology
Cannabinoid Receptor Modulators / physiology*
Conditioning, Classical / drug effects,  physiology
Corticosterone / administration & dosage,  pharmacology
Electroshock
Emotions / physiology
Endocannabinoids*
Fear / drug effects,  physiology*
Freezing Reaction, Cataleptic / physiology
Glucocorticoids / physiology*
Glycerides / physiology*
Hippocampus / drug effects,  physiology*
Male
Memory / drug effects,  physiology*
Morpholines / pharmacology
Naphthalenes / pharmacology
Piperidines / pharmacology
Propranolol / pharmacology
Pyrazoles / pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 / antagonists & inhibitors,  physiology*
Receptors, Glucocorticoid / physiology
Chemical
Reg. No./Substance:
0/AM 251; 0/Adrenergic beta-Antagonists; 0/Arachidonic Acids; 0/Benzoxazines; 0/Cannabinoid Receptor Modulators; 0/Endocannabinoids; 0/Glucocorticoids; 0/Glycerides; 0/Morpholines; 0/Naphthalenes; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 0/Receptors, Glucocorticoid; 134959-51-6/Win 55212-2; 50-22-6/Corticosterone; 525-66-6/Propranolol; 53847-30-6/2-arachidonylglycerol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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