PubMed:
Neuroscience. 2026 Nov 7:S0306-4522(26)00732-3. doi: 10.1016/j.neuroscience.2026.11.010. Online ahead of print.
ABSTRACT
The present study evaluated the pharmacological interaction of temozolomide (TMZ) chemotherapy with 3 potential antidepressant treatments (cannabidiol, CBD; fluoxetine, FLX; metformin, MET) in a rat glioblastoma model with the objective of finding drug combinations to better treat the depressive symptoms observed in glioblastoma patients. Methods Adult male Fisher 344 rats were inoculated with syngeneic RG2 cells into the right striatum. Then, rats received the antitumoral drug (TMZ, 25 mg/kg) vs. its vehicle (C-group), and 3 h later, treated with CBD (30 mg/kg), FLX (10 mg/kg), MET (100 mg/kg) or vehicle (Veh-group) for 5 days. The forced-swim test was used to score antidepressant-like responses. Markers of treatment response were evaluated in brain samples (hippocampal neurogenesis) of the non-tumor-infiltrated hemisphere and in blood plasma (corticosterone and immune system cells). Results The main results showed that TMZ alone and/or in combination with different types of potential antidepressants (CBD, FLX, MET) did not alter behavioral performance assessed in the forced-swim test. The absence of behavioral effects, however, is not attributed to a lack of pharmacological effects of the specific drugs. TMZ treatment decreased body weight gain, reduced the number of hippocampal neural progenitors and diminished immune plasma markers, while CBD and FLX decreased plasma corticosterone. Conclusion In conjunction, our results did not support the hypothesis of a beneficial use of antidepressants as a combinational therapy with TMZ to attenuate the most associated comorbidity of glioblastoma, depression, at least in male rats with this specific model of experimentally induced glioblastoma.
PMID:42998719 | DOI:10.1016/j.neuroscience.2026.11.010
