Background. Systemic administration of cannabidiol, a non-psychotomimetic component of Cannabis sativa, induces a rapid and maintained antidepressant effect in an animal model of depression. The medial prefrontal cortex, and more specifically the infralimbic cortex, have been associated to the fast antidepressant effect. However, the contribution of this important area to the effect of cannabidiol remains to be elucidated. Objectives. To analyze the effect of intra-infralimbic cannabidiol infusion on: (1) anxiety and depressive-like behaviors after 30 min and 24 h, and (2) the neuronal activation by c-Fos immunohistochemistry in the medial prefrontal cortex and the dorsal raphe nucleus in naïve and stressed animals.Results. Intra-infralimbic infusion of cannabidiol reduced immobility in the forced swimming test, by increasing the swimming behavior. No significant changes were observed in the open field test parameters relative to total distance and central activity. After two hours of cannabidiol infralimbic infusion, an increase in c-Fos expression in the dorsal raphe nucleus of naïve animals was observed. Moreover, cannabidiol also prevented the forced swimming test-induced increase of c-Fos labelling in the dorsal raphe nucleus and the infralimbic cortex. Conclusion. The antidepressant-like effect of cannabidiol infralimbic infusion appears to be correlated to the increase in neuronal activation in the dorsal raphe nucleus under basal conditions. In stressed animals, CBD prevented the neuronal activation in dorsal raphe nucleus and infralimbic cortex. Additional experiments are necessary to completely understand the CBD behavioral and molecular effects.
