Efeito do tratamento crônico com óleo de espectro completo de Cannabis sativa sobre comportamento tipo depressivo e o sistema purinérgico em ratos submetidos ao estresse no início da vida

Abstract

Depression is a multifactorial disease that can be related to the occurrence of stressful episodes in early life stages. From this perspective, there is the development of indifference towards activities considered objectively pleasurable, characterizing a depressive symptom called anhedonia. Additionally, depressive individuals may present a continuous state of irritability and long-term cognitive loss. Moreover, conventional treatments for depression are not completely effective in many cases. Therefore, this study aimed to analyze the therapeutic potential of full-spectrum Cannabis sativa oil (EC C. sativa) in rats subjected to maternal deprivation (PM) and social isolation (IS), as well as to investigate its effects on the purinergic system in peripheral blood mononuclear cells (PBMC), correlating them with possible increases in inflammation in the rats' bodies. Forty male Wistar rats were used in the experiment, thirty of which were subjected to ten days of PM in the early days of life and IS from the fiftieth day, while ten comprised the control group. Among the thirty rats subjected to stress protocols, ten rats received escitalopram treatment at a dosage of 10mg/Kg; ten rats received treatment with EC C. sativa oil at a dosage of 1mg/Kg. The control group rats received saline. After twelve days of pharmacological and saline treatment, the rats were subjected to the open field test (TCA), and after fourteen days of treatment, they were subjected to the forced swim test (TNF). After the last behavioral test, humane euthanasia was performed on these rats, followed by immediate blood and tissue collection for analysis. The FST results showed that, among the groups subjected to PM and IS, the group treated with EC C. sativa oil spent less time immobile compared to the stress-saline group. Thus, we evidenced a therapeutic potential in treating depression-like symptoms. Additionally, the group treated with the oil showed higher hydrolysis of the purinergic system biomarkers ATP, ADP, and AMP compared to all other groups. These results suggest increased activity of the ectonucleotidases CD39 and CD73, having physiological repercussions on purinergic receptor activation. The results suggest that EC C. sativa oil exerts an antidepressant-like effect. One of the possible biological mechanisms in which EC C. sativa oil acts is on purinergic markers in the extracellular medium, causing their greater hydrolysis. Therefore, Cannabis sativa phytopharmaceuticals may be a potential form of therapeutic use.