Efeito tipo antidepressivo do óleo de cannabis sativa de espectro completo na modulação do estresse oxidativo e sistema purinérgico em ratos submetidos a estresse no início da vida

Abstract

Major Depressive Disorder (MDD) has a complex and multifactorial etiology, where both traumatic events and chronic stress play significant roles, leading to neural and systemic biological dysfunctions. These factors can affect individuals from early developmental stages through to adulthood. Chronic stress during childhood impairs brain development, and when combined with a lack of social support in adulthood, it can lead to severe depression and resistance to antidepressant treatments. Clinical medications not only require a long time to manifest antidepressant effects but also fail to provide therapeutic benefits for a significant percentage of patients. Consequently, the search for more effective treatments for MDD has included medicinal plants as therapeutic strategies that may influence relevant biological mechanisms in this disorder. The objective of this study was to evaluate depressive-like behavior and mechanisms involved in the endocannabinoid system, purinergic system, and oxidative stress in rats subjected to maternal deprivation (MD) during early life, combined with social isolation (SI) in young adulthood, as well as to assess the effect of treatment with full spectrum C. sativa oil. Male Wistar rats were divided into four groups (N = 10 per group): Control without stress + saline; MD+SI + saline; MD+SI + Escitalopram; MD+SI + full spectrum C. sativa oil. The rats underwent the MD and SI stress model at the beginning of adulthood, except for the control group. Subsequently, they received chronic treatment for 14 days according to their group’s objective. At the end of the treatment, the animals were subjected to behavioral protocols assessing locomotor activity in the open field and mobility in the forced swimming test. After the behavioral tests, the animals were euthanized, and biological samples were collected for analysis of oxidative stress and purinergic system biomarkers. The MD+SI + saline group showed increased immobility time in the forced swimming test compared to the other groups, indicating that the MD+SI protocol induced depressive-like behavior. The stress protocol also induced oxidative stress in the MD + saline group, evidenced by increased MPO activity in plasma compared to the control + saline group. Treatment with full spectrum C. sativa oil reversed depressive-like behavior and reduced MPO activity and TBARS levels in plasma. Furthermore, the oil-treated group exhibited increased hydrolysis of purinergic system biomarkers ATP, ADP, and AMP compared to all other groups. These findings suggest enhanced activity of ectonucleotidases CD39 and CD73, which may have physiological effects on purinergic receptor activation. Therefore, chronic treatment with full spectrum C. sativa oil demonstrated significant modulatory effects on both oxidative stress and the purinergic system, contributing to the understanding of mechanisms involved in the treatment of MDD