The effect of Venlafaxine on the neuro-behavioral status of mice after administration of chemotherapeutic-neurotoxic agent (Cyclophosphamide)

Abstract

Background: Cyclophosphamide (CPH) is a cornerstone in cancer therapy and the present study explores the effect of Venlafaxine (VLX) against cognitive deficits induced by CPH in mice and its effect on neurogenesis in the hippocampus. Methods: Forty mice were randomly allocated to four groups: control, VLX, CPH, and CPH+VLX. The Novel Location Recognition model (NLR) test used here is a spatial variant of a two-trial object recognition task performed before and after the treatment with the drugs. Results: The control group, the VLX group, and the VLX and CPH group examined the object at the new location significantly more than the old one (P=0.04, P=0.05, and P=0.01, respectively). The test demonstrated a significant difference between Ki-67- positive cell numbers across the four groups (p < 0.0001). There was a significant decrease in the total number of Ki67-positive cells in the CPH group compared to the control group (p < 0.001). Conversely, the combined CPH and VLX group showed increased hippocampal proliferation compared to the CPH group (p < 0.001). There was a significant difference between GPX-1 positively stained cell numbers between control and CPH as well as control and CPH+VLX treated cells (p < 0.001) for both. Conclusion: our results show that CPH treatment caused cognitive deficits which were associated with a reduction in cell proliferation in dentate gyrus. These deficits were reduced when VLX was administered along with CPH.