Efeitos dos óleos de cannabis sativa sobre comportamento tipo depressivo e a expressão de BDNF no hipocampo de ratos machos submetidos a estresse na infância

Abstract

Major depressive disorder (MDD) is a multifactorial condition involving biological, psychological, and environmental changes, with early stress being one of the most relevant factors for the development of neural and systemic dysfunctions. Among the animal models used to investigate these mechanisms, maternal deprivation (MD) and social isolation (SI) stand out for mimicking adverse experiences in childhood and adolescence. Given the limitations and resistance to traditional antidepressants such as escitalopram, which have a slow onset of action and limited efficacy in a significant portion of patients, compounds derived from Cannabis sativa, especially cannabidiol (CBD), have been studied as promising therapeutic alternatives for stress- and depression-related disorders. This study investigated the effects of chronic treatment with isolated cannabidiol oil (30 mg/kg) and full spectrum oil (1 mg/kg) on depressive-like behaviors and brain-derived neurotrophic factor (BDNF) levels in the hippocampus of 55 male Wistar rats subjected to MD and SI. The animals were subjected to MD from the 1st to the 10th day of life and SI in young adulthood, approximately between the 50th and 80th day. The experimental groups were distributed as follows: (1) control, without exposure to stress, treated with vehicle; (2) MD + SI, treated with vehicle; (3) MD + SI, treated with escitalopram (10 mg/kg); (4) MD + SI, treated with full-spectrum Cannabis sativa oil (1 mg/kg); and (5) MD + SI, treated with oil containing isolated cannabidiol (30 mg/kg). All treatments were administered orally for 14 days. The animals were evaluated using the Open Field Test (OFT) and the Forced Swimming Test (FST), in addition to biochemical analyses of BDNF levels. The results demonstrated that early stress significantly increased immobility in the FST and reduced BDNF levels in the hippocampus, confirming the efficacy of the MD and SI models in inducing a depressive-like phenotype. Treatment with escitalopram (10 mg/kg) and isolated CBD (30 mg/kg) reduced immobility time, while full-spectrum oil had no significant effect (1 mg/kg). In the TCA, no locomotor changes were observed between groups. Despite behavioral improvement, none of the treatments tested reversed the decrease in hippocampal BDNF levels. It is concluded that the combination of MD and SI generates behavioral and neurobiological changes consistent with MDD, and that isolated cannabidiol has a behavioral antidepressant effect, although it did not restore BDNF expression in the hippocampus under the conditions tested. These findings reinforce the therapeutic potential of CBD as an alternative in the management of major depressive disorder.