Abstract
Vincristine is a commonly used cytostatic drug for the treatment of leukemia, neuroblastoma and lung cancer, which is known to have neurotoxic properties. The aim of this study was to assess the effects of vincristine, injected directly into the dorsal hippocampus, in spatial memory using the spatial cone field discrimination task. Long Evans rats were trained in the cone field, and after reaching training criterion received bilateral vincristine infusions into the dorsal hippocampus. Vincristine-treated animals presented unilateral or bilateral hippocampal lesions. Animals with bilateral lesions showed lower spatial working and reference memory performance than control animals, but task motivation was unaffected by the lesions. Working and reference memory of animals with unilateral lesions did not differ from animals with bilateral lesions and control animals. In sum, intrahippocampal injection of vincristine caused profound tissue damage in the dorsal hippocampus, associated with substantial cognitive deficits.
Highlights
Vincristine is a vinca alkaloid obtained from the plant Catharanthus roseus commonly used as a chemotherapeutic agent in veterinary and human practice, for the treatment of acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin’s disease, neuroblastoma, and small cell lung cancer [1, 2], among others
The aim of this study was to assess the effects of intrahippocampal injection of vincristine into the dorsal hippocampus, a brain structure implicated in spatial memory, and to assess the sensitivity of the spatial cone field discrimination task in detecting cognitive deficits caused by hippocampal lesions
Surgery affected overall working memory performance (F2,105 = 5.90, p = 0.0037): the bilateral lesion group showed a lasting lower working memory performance than the control group, but no differences were observed between both groups and the unilateral lesion group
Summary
Vincristine is a vinca alkaloid obtained from the plant Catharanthus roseus commonly used as a chemotherapeutic agent in veterinary and human practice, for the treatment of acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin’s disease, neuroblastoma, and small cell lung cancer [1, 2], among others. Vincristine is a neurotoxic chemotherapeutic agent known to produce sensory and motor, as well as autonomic neuropathies [3]. Disturbance of the microtubule formation stops mitosis, directly affecting all rapidly dividing cells, such as cancer cells [7]. A recent study assessing the effect of vincristine on neural tissue concluded that vincristine causes dose-dependent neurotoxicity through the inhibition of the expression of microtubule-related proteins such as tubulin and fribronectin, and the downregulation of the gene matrix metalloproteinase-10 [8].
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