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Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory.
Proc Natl Acad Sci U S A. 2012 Feb 28; 109(9):3504-9.PN

Abstract

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+Show Affiliations

Department of Neuroscience, Section Anatomy, University Medical Center Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands. pirayy@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

22331883

Citation

Atsak, Piray, et al. "Glucocorticoids Interact With the Hippocampal Endocannabinoid System in Impairing Retrieval of Contextual Fear Memory." Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 9, 2012, pp. 3504-9.
Atsak P, Hauer D, Campolongo P, et al. Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory. Proc Natl Acad Sci USA. 2012;109(9):3504-9.
Atsak, P., Hauer, D., Campolongo, P., Schelling, G., McGaugh, J. L., & Roozendaal, B. (2012). Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory. Proceedings of the National Academy of Sciences of the United States of America, 109(9), 3504-9. https://doi.org/10.1073/pnas.1200742109
Atsak P, et al. Glucocorticoids Interact With the Hippocampal Endocannabinoid System in Impairing Retrieval of Contextual Fear Memory. Proc Natl Acad Sci USA. 2012 Feb 28;109(9):3504-9. PubMed PMID: 22331883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory. AU - Atsak,Piray, AU - Hauer,Daniela, AU - Campolongo,Patrizia, AU - Schelling,Gustav, AU - McGaugh,James L, AU - Roozendaal,Benno, Y1 - 2012/02/13/ PY - 2012/2/15/entrez PY - 2012/2/15/pubmed PY - 2012/5/9/medline SP - 3504 EP - 9 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 109 IS - 9 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/22331883/Glucocorticoids_interact_with_the_hippocampal_endocannabinoid_system_in_impairing_retrieval_of_contextual_fear_memory_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=22331883 DB - PRIME DP - Unbound Medicine ER -