Faculty Collaboration Database

Role of beta-catenin and endocannabinoids in the nucleus accumbens in extinction in rats exposed to shock and reminders. Neuroscience 2017 Aug 15;357:285-294

Date

06/19/2017

Pubmed ID

28624572

DOI

10.1016/j.neuroscience.2017.06.015

Scopus ID

2-s2.0-85021388226 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

The response to a traumatic experience may be rapid recovery or development of psychopathology such as post-traumatic stress disorder (PTSD). Impaired extinction of fear memories is thought to contribute to the development of the persistent trauma memories and avoidance. The Wnt/β-catenin pathway and the endocannabinoid system appear to play significant roles in anxiety and depressive symptoms. Here we examined the involvement of β-catenin in the nucleus accumbens (NAc) in extinction in rats exposed to the shock and reminders model of PTSD. We found that increased β-catenin levels in the NAc were correlated with facilitated extinction kinetics in rats exposed to shock and reminders, suggesting that increased levels of NAc β-catenin are associated with a resilient response to the stressor. Furthermore, downregulating β-catenin expression in the NAc in shocked rats using sulindac (0.0178, 0.178mg/side) impaired extinction whereas upregulating the Wnt/β-catenin pathway using LiCl (2µg/side) facilitated extinction. Exposure to shock and reminders resulted in attenuated levels of the endocannabinoid N-arachidonylethanolamine (AEA) in the NAc; the cannabinoid CB1/2 receptor agonist WIN55,212-2 (5µg/side) microinjected into the NAc facilitated extinction in shocked rats. Importantly, the facilitating effect of WIN55,212-2 on extinction was blocked by co-administration of sulindac in doses that downregulated β-catenin levels. Taken together, the results suggest that β-catenin in the NAc may serve as a protective buffer against the effects of severe stress, and that inhibiting this system in the NAc may prevent the therapeutic effects of cannabinoids against stress-related disorders.

Author List

Korem N, Lange R, Hillard CJ, Akirav I

Author

Cecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Benzoxazines
Cannabinoid Receptor Agonists
Electroshock
Endocannabinoids
Extinction, Psychological
Male
Morpholines
Naphthalenes
Nucleus Accumbens
Rats, Sprague-Dawley
Receptors, Cannabinoid
Resilience, Psychological
Stress Disorders, Post-Traumatic
Stress, Psychological
beta Catenin