The effects of the antineoplastic drugs vincristine, maytansine and cis-platinum were studied to determine the appropriateness of a behavioral and electrophysiological test battery for characterizing the neurotoxicity of such therapeutic compounds. Single- and repeated-dose studies in rats were performed initially, to establish doses for the subchronic neurobehavioral study. Measurements obtained in the subchronic study included body weight, rectal temperature, forelimb and hindlimb grip strengths; performance of a multisensory conditional avoidance response task and other behavioral tests; and a series of evoked responses (ventral caudal nerve action potential, brainstem auditory response and responses from other modalities). The drugs were injected intraperitoneally 5 days per week for 7 weeks. The rats were tested weekly during baseline, treatment and recovery phases. Each drug caused a different pattern of effects, but they all altered body weight, rectal temperature, peripheral nerve conduction velocity, the somatosensory evoked potential and undifferentiated motor activity. cis-Platinum was the most toxic, and maytansine was the least toxic. The results indicated that some elements of the test battery were useful for evaluating the neurotoxicity of anticancer drugs. However, other tests - notably, a test of negative geotaxis and the cortical auditory evoked response - were unreliable.
Minimal, maximal, or sham seizures were chronically administered to 168 male Wistar rats 3 or 5 times per week for 4,8,12, or 16 wk. Regional analysis of the brains revealed that increase in weight of the whole brain of electroshocked Ss reported previously was confined to the cortex-especially ventral cortex, including hippocampus and amygdala. Total protein and total AChE actively increased throughout most of the brain in proportion to increase in weight. Specific ChE activity decreased in the cortex of electroshocked Ss, especially visual and ventral cortex. Electroshocked Ss given maximal seizures 5 times per week performed more poorly than controls on a spatial discrimination test in an underwater T maze.
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