Exploring the antidepressant-like effects of cannabidiol and/or temozolomide in female mice with induced glioblastoma.

Abstract

Temozolomide (TMZ), the gold standard drug used for the treatment of glioblastoma, is known to affect healthy brain proliferating cells, inhibiting adult hippocampal neurogenesis. Since most antidepressants mediate their beneficial effect through this process and given the large proportion of glioblastoma patients with depressive symptoms, this preclinical study evaluated the interaction between TMZ and cannabidiol (CBD), a cannabinoid compound with antidepressant-like potential. To do so, adult female nude mice were intracranially implanted with GL261 tumor cells and treated with TMZ (5 mg/kg) or PBS twice a week. Additionally, animals received CBD (30-45 mg/kg) 5 days/week (1 dose/day) rendering two groups (PBS-CBD vs. TMZ-CBD). To control for the effects of TMZ alone a group of mice was treated with vehicle (TMZ-Veh). MRI was used to evaluate tumor growth and/or its suppression by treatment. Antidepressant-like responses were assessed under stressful settings (forced-swim or tail-suspension tests) and brain samples were collected to evaluate hippocampal neuroplasticity/neurotoxicity markers. The main results showed that the combined treatment with TMZ-CBD decreased tumor volume, induced signs of antidepressant-like responses, while modulated hippocampal FADD as compared to PBS-CBD female mice. However, these effects were no different than the ones observed by TMZ-Veh, suggesting that TMZ alone was sufficient to observe the behavioral and neurochemical responses, and that adding a concomitant CBD treatment did not change that outcome. This data adds to our recent studies suggesting some beneficial affective-like responses induced by TMZ in rodents, while validating them in a female mice model with induced glioblastoma.