The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory
Open accessAbstract
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.
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“As part of this protective role under aversive conditions, elevated EC signaling during stress has been shown to dampen the development of anxiety [12] and to regulate the encoding [13], retrieval [14] and extinction [15] of traumatic memories.”
From Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder (2013) · cites this paper as [14]
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Metadata
- Authors
- Atsak, P., Hauer, D., Campolongo, P., Schelling, G., McGaugh, J. L., & Roozendaal, B.
- Affiliations
- University Medical Center Groningen (NL)
- Sapienza University of Rome (IT)
- Ludwig-Maximilians-Universität München (DE)
- University of California, Irvine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-02-13
- Volume
- 109
- Issue
- 9
- Pages
- 3504-3509
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3295257
- OpenAlex
- W2147317037
- Cited by
- 140
- References
- 64
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 13 · 2016: 12 · 2015: 16 · 2014: 14 · 2013: 11 · 2012: 5
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glucocorticoids, endocannabinoid system, hippocampus, contextual fear memory, corticosterone, CB1 receptor, 2-arachidonoylglycerol, noradrenergic activity, propranolol, beta-adrenoceptor antagonism, WIN 55,212-2, emotional arousal, retrograde signaling
- MeSH terms
- Acoustic Stimulation, Adrenergic beta-Antagonists, Animals, Arachidonic Acids, Arousal, Conditioning, Classical, Corticosterone, Electroshock, Emotions, Fear, Glucocorticoids, Glycerides, Hippocampus, Male, Memory, Morpholines, Naphthalenes, Piperidines, Propranolol, Pyrazoles, Receptors, Glucocorticoid, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1, Freezing Reaction, Cataleptic, Benzoxazines, Rats, Cannabinoid Receptor Modulators, Endocannabinoids
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