The response to a traumatic experience may be rapid recovery or development of psychopathology such as posttraumatic 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-cateninpathway using LiCl (2 µg/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 (5 µg/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.
Copyright © 2017. Published by Elsevier Ltd.
Endocannabinoids; Extinction; Nucleus accumbens; PTSD; WIN55,212-2; β –catenin
- PMID: 28624572
- DOI: 10.1016/j.neuroscience.2017.06.015