Efeitos do estresse de privação maternal e isolamento social em comportamentos depressivos e ansiosos: potencial terapêutico dos óleos de Cannabis sativa em modelos animais

Abstract

Major Depressive Disorder (MDD) is a multifactorial disorder in which childhood traumatic events and chronic stress play central roles in the dysregulation of neuroplasticity. The resistance to conventional antidepressant treatments, which exhibit slow onset of action and limited efficacy in a significant portion of patients, has driven the search for new therapies, including the use of compounds derived from Cannabis sativa. This study investigated the effects of chronic treatment with full-spectrum and isolated cannabidiol (CBD) Cannabis sativa oils on depressive- and anxiety-like behaviors, as well as the hippocampal protein expression of cannabinoid type 1 receptors (CB1R) and brain-derived neurotrophic factor (BDNF) in a dual-stress model: maternal deprivation (MD) and social isolation (SI). A total of 110 Wistar rats (55 males and 55 females) were used. Animals were subjected to MD during the first days of life (PND 1–10) and SI during adolescence (approximately PND 50–80). The animals were divided into five groups: Control (C+CT); Stress + Vehicle (E+CT); Stress + Escitalopram (E+ESC; 10 mg/kg); Stress + Full Spectrum Oil (E+FS; 1 mg/kg); and Stress + Isolated CBD (E+CBD; 30 mg/kg). Treatments were administered orally for 14 days. Depressive- and anxiety-like behaviors were assessed through forced swimming and elevated plus maze tests, respectively. The results indicate that MD and SI induce depressive and anxious behaviors in rats. Isolated CBD (30 mg/kg) reversed these effects in males, while in females, both isolated CBD (30 mg/kg) and full-spectrum oil (1 mg/kg) were effective. Biochemical analyses of the hippocampus showed that, in males, the MD and SI protocol significantly reduced BDNF and CB1R levels. While none of the treatments were effective in restoring BDNF concentrations, treatment with isolated CBD and full-spectrum oil restored CB1R levels to control values. In contrast, in females, stress did not alter baseline BDNF or CB1R levels. However, interventions with isolated CBD (30 mg/kg) and full-spectrum oil (1 mg/kg) promoted a downregulation of BDNF levels in the female hippocampus, while full-spectrum oil (1 mg/kg) induced an upregulation of the CB1 receptor.