Corticosteroid-endocannabinoid loop supports decrease of fear-conditioned response in rats.
The endocannabinoid (eCB) and glucocorticoid systems contribute to the modulation of emotional states. Noteworthy, glucocorticoid hormones are released by adrenal glands during stressful events and endocannabinoids are released in the brain during fear-conditioned responses. Since it was already suggested that glucocorticoids may trigger the release of endocannabinoids in the brain, our objective was to investigate whether the interaction between these neuromodulatory systems contributes to the decrease of conditioned freezing behavior over successive 9-min exposures to the conditioning context. Present results suggest a bidirectional interdependence between glucocorticoid and endocannabinoid systems. CB1 receptors blockade prevents glucocorticoid-induced facilitation of conditioned freezing decrease and inhibition of glucocorticoid synthesis renders boosting of endocannabinoid signaling innocuous, while preserving the efficacy of direct CB1 receptors activation by an exogenous cannabinoid agonist. This suggests that CB1 receptors are somehow "downstream" to glucocorticoid release, which in its turn, is reduced by CB1 activation, contributing to the persistent reduction of conditioned freezing responses.
Laboratory of Psychopharmacology, Pharmacology Department, Universidade Federal de Santa Catarina, Florianopolis 88049-900, Brazil. Electronic address: farmariano@bol.com.br.
R M
RM
Bitencourt
D'Or Institute for Research and Education, Rio de Janeiro 22230-100, Brazil.
F A
FA
Pamplona
Laboratory of Psychopharmacology, Pharmacology Department, Universidade Federal de Santa Catarina, Florianopolis 88049-900, Brazil.
R N
RN
Takahashi
D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism*; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects*; D046352:Freezing Reaction, Cataleptic; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D013148:Spironolactone / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D001095:Arachidonic Acids; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D000451:Mineralocorticoid Receptor Antagonists; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011965:Receptors, Glucocorticoid; D013148:Spironolactone; D015735:Mifepristone; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003907:Dexamethasone; D000077285:Rimonabant; C107594:N-(4-hydroxyphenyl)arachidonylamide; D008797:Metyrapone
Cannabinoid; Extinction; Fear conditioning; Glucocorticoid