The effects of cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala and hippocampus on the consolidation of a traumatic event.

Abstract

Ample evidence demonstrates that fear learning contributes significantly to many anxiety pathologies including post-traumatic stress disorder (PTSD). The endocannabinoid (eCB) system may offer therapeutic benefits for PTSD and it is a modulator of the hypothalamic pituitary adrenal (HPA) axis. Here we compared the separated and combined effects of blocking glucocorticoid receptors (GRs) using the GR antagonist RU486 and enhancing CB1r signaling using the CB1/2 receptor agonist WIN55,212-2 in the CA1 and basolateral amygdala (BLA) on the consolidation of traumatic memory. Traumatic memory was formed by exposure to a severe footshock in an inhibitory avoidance apparatus followed by exposure to trauma reminders. Intra-BLA RU486 (10ng/side) and WIN55,212-2 (5μg/side) administered immediately after shock exposure dampened the consolidation of the memory about the traumatic event and attenuated the increase in acoustic startle response in rats exposed to shock and reminders. In the CA1, WIN55,212-2 impaired consolidation and attenuated the increase in acoustic startle response whereas RU486 had no effect. The effects of WIN55,212-2 were found to be mediated by CB1 receptors, but not by GRs. Moreover, post-shock systemic WIN55,212-2 (0.5mg/kg) administration prevented the increase in GRs and CB1 receptor levels in the CA1 and BLA in rats exposed to shock and reminders. The findings suggest that the BLA is a locus of action of cannabinoids and glucocorticoids in modulating consolidation of traumatic memory in a rat model of PTSD. Also, the findings highlight novel targets for the treatment of emotional disorders and PTSD in particular.

• Authors: Noa Shoshan, Irit Akirav
• Journal: Neurobiology of learning and memory (Neurobiol Learn Mem) Vol. 144 Pg. 248-258 (Oct 2017) ISSN: 1095-9564 [Electronic] United States
• PMID: 28818702 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Benzoxazines
• Morpholines
• Naphthalenes
• Receptor, Cannabinoid, CB1
• Receptors, Glucocorticoid
• Mifepristone
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone

Topics

• Amygdala (drug effects, physiology)
• Animals
• Benzoxazines (administration & dosage)
• Disease Models, Animal
• Electroshock
• Extinction, Psychological
• Fear
• Hippocampus (drug effects, physiology)
• Male
• Memory Consolidation (drug effects, physiology)
• Mental Recall
• Mifepristone (administration & dosage)
• Morpholines (administration & dosage)
• Naphthalenes (administration & dosage)
• Rats, Sprague-Dawley
• Receptor, Cannabinoid, CB1 (agonists, physiology)
• Receptors, Glucocorticoid (antagonists & inhibitors, physiology)
• Reflex, Startle
• Stress Disorders, Post-Traumatic (physiopathology, psychology)