The endocannabinoid, anandamide, modulates anxiety-like behaviours in young, male rats

Abstract

Anxiety disorders are a major psychological health concern in society today and while treatments are available that target neurotransmitters such as GABA and serotonin, they are known to cause adverse effects. Other neurotransmitters, like endocannabinoids (eCBs) and nitric oxide (NO), have been shown to modulate anxiety-like behaviours; however, the mechanisms regarding how eCBs and NO affect anxiety in youth remains unclear. Many studies have highlighted the importance of the eCB anandamide in the modulation of anxiety and the stress response. Thus, the purpose of this study was to further investigate eCBs, specifically anandamide, and NO in young rats. We hypothesized that anandamide will modulate anxious behaviours in a CB1 receptor and NO dependent manner. In order to investigate this hypothesis, young male Sprague-Dawley rats were placed into one of the following treatment groups: 1) vehicle (saline), 2) URB597 (fatty acid amide hydrolase (FAAH) inhibitor), 3) vehicle (30-minute restraint), 4) URB597 (30-minute restraint), 5) L-NAME (blocks NO synthesis, 30-minute restraint), 6) URB597 + L-NAME (30-minute restraint), 7) SR141716 + URB597 (cannabinoid 1 (CB1) receptor antagonist, 30-minute restraint), and their anxiety was tested using the elevated plus-maze. There were no statistically significant differences observed between nonstressed experimental groups (vehicle and URB597). Administration of URB597 prior to acute stress significantly decreased open arm time in the maze, reflecting anxiogenic behaviour. In the presence of the CB1 receptor antagonist or the NO synthesis blocker, URB597 significantly increased anxious behaviours. These findings suggest that anandamide may have anxiogenic-like effects following acute stress in which CB1 receptors and NO does not play a role.