Quantificação do receptor canabinóide tipo 1 hipocampal e análise de comportamentos tipo ansioso e depressivo em ratos machos submetidos à privação maternal e isolamento social tratados com óleos de Cannabis Sativa

Abstract

Major depressive disorder (MDD) is a multifactorial psychiatric disorder associated with neurobiological alterations resulting from the interaction between genetic and environmental factors. Adverse experiences, such as maternal deprivation and social isolation, may induce persistent alterations in circuits involved in emotional regulation, including modifications in the endocannabinoid system. In this context, Cannabis sativa-derived compounds have been investigated due to their therapeutic potential in modulating stress-related behavioral and neurobiological alterations. The present study evaluated the effects of chronic treatment with isolated cannabidiol (CBD) oil and full-spectrum Cannabis sativa oil on anxiety-like and depressive-like behaviors and hippocampal cannabinoid receptor type 1 (CB1R) levels in male Wistar rats subjected to maternal deprivation (MD) and social isolation (SI). Fifty-five rats were distributed into five experimental groups: Control + vehicle (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). MD was performed during the first 10 days of life, whereas SI occurred during young adulthood for 30 consecutive days. Following the stress protocol, animals received oral treatment for 14 days. Exploratory and locomotor behaviors were evaluated using the open field test, anxiety-like behaviors using the elevated plus maze, and depressive-like behaviors using the forced swimming test. Hippocampal CB1R levels were determined by ELISA assay. The results demonstrated that combined exposure to MD and SI induced behavioral alterations, characterized by increased anxiety-like and depressive-like behaviors, as well as reduced hippocampal CB1R levels compared with the control group. Treatment with isolated CBD was able to reverse these alterations, reducing anxiety-like and depressive-like behaviors and restoring hippocampal CB1R levels. In contrast, full-spectrum oil treatment increased hippocampal CB1R levels, suggesting modulation of the endocannabinoid system; however, it was unable to reverse stress-induced behavioral impairments under the evaluated conditions. These findings indicate that isolated CBD has therapeutic potential for modulating behavioral and neurobiological alterations associated with early-life stress.