Circadian Influence on Acute Stress-induced Changes in Cortico-limbic Endocannabinoid Levels in Adult Male Rats

Abstract

The endocannabinoid (eCB) system plays an important role in regulating the stress response, including glucocorticoid release and the generation of avoidance behaviour. Its two major ligands, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide; AEA), are dynamically influenced by psychological stress to gate the generation of the stress response and facilitate recovery upon stress termination. Many biological systems exhibit circadian "daily" rhythms, including glucocorticoids and endocannabinoids, and the behavioural and endocrine impact of stress is modulated by the time of day. Nonetheless, most preclinical experiments investigating the interaction between stress and endocannabinoids occur in the light, "inactive" phase. We therefore tested if circadian phase influences stress-induced changes in eCB levels in the hippocampus (HIP), prefrontal cortex (PFC), and amygdala (AMY). Adult male rats were exposed to 15 min swim stress or immediately euthanized, and brains were collected. Testing occurred either early in the light or early in the dark phase of their cycle to compare circadian effects. We found that overall, stress decreased AEA in the AMY and HIP, with an effect in the PFC dependent on the time of day. Conversely, stress increased 2-AG in the AMY, with an effect in the PFC and HIP dependent on the time of day. This suggests that stress has a similar overall impact on eCB levels regardless of circadian phase, but that subtle differences may occur depending on the brain region, especially the PFC.

Keywords: 2-AG; anandamide; circadian; endocannabinoid; stress.