title: Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory.
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.affiliation: Department of Neuroscience, Section Anatomy, University Medical Center Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands. pirayy@gmail.com
authors.forename: Piray
authors.initials: P
authors.lastname: Atsak
authors.forename: Daniela
authors.initials: D
authors.lastname: Hauer
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
authors.forename: James L
authors.initials: JL
authors.lastname: McGaugh
authors.forename: Benno
authors.initials: B
authors.lastname: Roozendaal
mesh_terms: D000161:Acoustic Stimulation; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology*; D001143:Arousal / Q000502:physiology; D048588:Benzoxazines / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology; D004597:Electroshock; D004644:Emotions / Q000502:physiology; D063388:Endocannabinoids; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology*; D005989:Glycerides / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D001095:Arachidonic Acids; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005938:Glucocorticoids; D005989:Glycerides; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011965:Receptors, Glucocorticoid; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094503:glyceryl 2-arachidonate; D011433:Propranolol; D003345:Corticosterone