| Autor: |
Kim HJJ; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Zagzoog A; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Ceni C; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.; Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.; Doctoral School in Life Sciences, University of Siena, 53100 Siena, Italy., Ferrisi R; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.; Department of Pharmacy, University of Pisa, 56126 Pisa, Italy., Janz N; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Laprairie RB; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.; Department of Pharmacology, College of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada. |
| Abstrakt: |
The endocannabinoid and orexin systems share many biological functions, including wakefulness, stress response, reward processing, and mood. While these systems work against one another with respect to arousal, chronic stress-induced downregulation of both systems often leads to anhedonia or the inability to experience pleasure from natural rewards. In the current study, a 24 h restraint stress test (24 h RST) reduced sucrose preference in adult male and female C57BL/6 mice. Prior to the stressor, subsets of mice were intraperitoneally administered cannabinoid and orexin receptor agonists, antagonists, and combinations of these drugs. Restraint mice that received the cannabinoid receptor type 1 (CB1R) antagonist SR141716A, orexin receptor type 2 (OX2R) agonist YNT-185, and the combination of SR141716A and YNT-185, exhibited less anhedonia compared to vehicle/control mice. Thus, the 24 h RST likely decreased orexin signaling, which was then restored by YNT-185. Receptor colocalization analysis throughout mesocorticolimbic brain regions revealed increased CB1R-OX1R colocalization from SR141716A and YNT-185 treatments. Although a previous study from our group showed additive cataleptic effects between CP55,940 and the dual orexin receptor antagonist (TCS-1102), the opposite combination of pharmacological agents proved additive for sucrose preference. Taken together, these results reveal more of the complex interactions between the endocannabinoid and orexin systems. |
