Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats

Introduction: The present study examined the effects of fatty acid amide hydrolase inhibitor URB597 on the level of plasma catecholamine and their content, synthesis, and degradation in the adrenal medulla of male and female rats subjected to chronic unpredictable stress (CUS). Material and Methods: Male and female Wistar rats were exposed to the 6 weeks of CUS and treated intraperitoneally with either 0.3 mg/kg/day of URB597 or vehicle in the last 2 weeks of stress protocol. Catecholamines' plasma levels and catecholamines' levels in adrenal medulla were examined using Elabscience ELISA kits. Western blot analysis was used to detect the protein in the medulla. Results: The results of our experiment showed that adrenal weights and catecholamine of unstressed control were higher in females and that CUS induced further enlargement of adrenal glands and catecholamine content and its synthesis compared to male rats. CUS caused an increase of plasma norepinephrine and depletion of norepinephrine content as well as unchanged synthesis and degradation of catecholamine in the adrenal medulla of male rats. URB597 reduced enlarged adrenals and catecholamine content and its synthesis in stressed female rats. URB597 reduces increased plasma norepinephrine and restores its content in the adrenal medulla, unchanging the expression of enzyme synthesis, while reduced protein levels of monoamine oxidase A in male rats are exposed to CUS. Discussion: Our results support the role of endocannabinoids as an antistress mechanism that inhibits elevated adrenomedullary activation and promotes its recovery to baseline in both male and female stressed rats.

Automated summary

The study investigated the effects of the fatty acid amide hydrolase inhibitor URB597 on plasma catecholamine levels and their synthesis and degradation in the adrenal medulla of male and female rats under chronic unpredictable stress. Results showed that URB597 reduced catecholamine content and synthesis in stressed female rats, while females had higher adrenal weights and catecholamine levels before stress than males, and stress further increased these levels in females compared to males. Additionally, the inhibitor reduced plasma norepinephrine levels and restored content in the adrenal medulla in male rats under stress. The findings suggest a potential role for endocannabinoids in modulating stress response in both male and female subjects.