*Astrid P. Ramos-Rolón, Wickensonn Norze, Paula A. Muñoz-Rodríguez, Amanda I. Rodríguez-Leon, Paola

Eusebio Severino, Kristie M. Torres-Montero, Keimarie Berrios-Rodríguez, Alexander I. Acevedo-Jetter, Valeria

M. Schleier-Albino, Miciely C. Aponte-Reyes, C. S. Maldonado-Vlaar

University of Puerto Rico-Rio Piedras, Department of Biology, PO BOX 23360, San Juan, Puerto Rico. 1 University

of Puerto Rico-Rio Piedras, Department of Biology, PO BOX 23360, San Juan, Puerto Rico.

Depression is one of the most prevalent mental health disorders in the United States. Studies have shown that the endocannabinoid system (eCB) has been implicated in the pathophysiology of depression. The cannabinoid-1 receptor (CB1) plays a role in depression-like behavior by modulating the serotonergic system. Other studies have revealed that aerobic exercise decreases depression-like behavior by upregulating serotonin (5-HT) release. However, it is still unknown if the eCB system modulates the antidepressive properties of exercise through an alteration in 5-HT firing. This project aims to observe if manipulating the CB1 receptor would enhance the therapeutic effect of aerobic exercise in depression. We hypothesized that the eBC system’s activation modulates 5-HT firing mediating antidepressive properties of exercise. Male Sprague Dawley rats were exposed to an aerobic exercise protocol, while a group remained sedentary.

Within the sedentary and exercise group, some rats received intraperitoneal injections of an agonist of the eCB receptors, (+)-WIN 55,212-2, while the others received control injections. The rats were divided into four groups: sedentary with the vehicle (Sed/Veh), sedentary with WIN55,212-2 (Sed/WIN), exercise with the vehicle (Exe/Veh), and exercise with WIN55,212-2 (Exe/WIN). We used the forced swim test (FST) paradigm as an animal model that characterizes depression-like behaviors in rodents. The FST results showed no significant differences of the agonist treatment between the group that experienced exercise vs. the sendentary group. We also performed western blots to quantify the concentration of the CB1 receptors and the 5-HT 1A receptors within limbic brain regions such as the hippocampus and medial prefrontal cortex. No significant differences regardless of treatment were detected for the CB1 receptor and the 5-HT 1A receptor in both the hippocampus and medial prefrontal cortex. The present studies did not detect a potential cross talk between eCB and 5HT in the anti-depressive effects of exercise.

Further studies are needed to better understand potential molecular mechanisms involved in new treatments for depression.

Keywords: Endocannabinoid system, depression, serotonin, and aerobic exercise

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