Efeito do óleo de Canabidiol sobre comportamento tipo depressivo e nível de Interleucina-6 na amígdala de ratos machos adultos submetidos a estresse precoce

Abstract

Major Depressive Disorder is a multifactorial and highly prevalent psychiatric condition associated with significant impacts on quality of life and public health. Among the most relevant risk factors for the development of depressive disorders is exposure to stressors during critical periods of development, such as childhood and adolescence, which can promote persistent neurobiological alterations. Evidence indicates that neuroinflammatory processes, including the involvement of pro-inflammatory cytokines such as interleukin-6 (IL-6), may contribute to the pathophysiology of these alterations. In this context, compounds derived from Cannabis sativa, such as cannabidiol (CBD), have attracted growing interest due to their therapeutic potential, particularly because of their antidepressant-like and immunomodulatory properties. Thus, this study aimed to evaluate the effects of sequential exposure to maternal deprivation during the early postnatal period and social isolation during adolescence on depressive-like behavior and IL-6 levels in the amygdala of adult male Wistar rats, as well as the effects of treatment with CBD oil compared with escitalopram. Depressive-like behavior was assessed using the splash test, while IL-6 levels were determined by enzyme-linked immunosorbent assay (ELISA). The results demonstrated that exposure to the early- life stress protocol significantly reduced grooming time, indicating behavioral alterations compatible with depressive-like behavior. Treatment with both CBD and escitalopram significantly improved this behavior. Regarding neuroinflammatory analysis, no significant differences in IL-6 levels were observed between the control and stress groups. However, CBD treatment significantly reduced IL-6 levels in the amygdala, an effect not observed with escitalopram. These findings suggest that sequential exposure to maternal deprivation and social isolation induces behavioral alterations associated with depressive-like phenotypes in adult male Wistar rats. In addition, CBD demonstrated potential therapeutic effects by improving behavior and modulating an inflammatory marker, suggesting possible immunomodulatory action in experimental models related to early-life stress.