The Development of a Behavioral Model for Ischemia in Rats
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Stroke, or focal cerebral ischemia, is of great clinical importance. When oxygenated, nutrient rich, blood supply to the brain is reduced and not resumed within the revival time of the brain cells, energy metabolism and all endergonic processes break down, leading to cell death (Hossman, 1989). In experimental models of stroke, (e.g. carotid occlusion in rats) neuroprotection can be obtained using pharmacological agents such as excitatory amino acid antagonists (Sauer et aI., 1989), calcium channel blockers (Hossman, 1989), and by Phencyclidine (Ikin et aI., 1990). The present experiments are pilot studies that detailed the behavioral effects of cerebral ischemia in experimentally naive Long Evans rats. Forebrain ischemia was produced by bilateral occlusion of the common carotid arteries in combination with systemic hypoxia (Pulsinelli and Brierley, 1978). Behavioral baselines measuring motor control, sensitivity to stimuli, learning, and memory were established to assess the effects of the ischemic insult on the rats. The behavioral assays examining motor control and sensory stimulation proved to be insensitive measures to the effects of ischemia, and besides tracking the weight of the animals they will not be included in future studies. Utilizing three different schedules of reinforcement (e.g. Fixed-Ratio 20 key press, Fixed-Ratio 20 lever press, and DRL 15"), operant conditioning provided a measure of learning and memory. The schedules of reinforcement (Ferster and Skinner, 1957) also provided a means for the study of the effects of a neuroprotector (e.g. Phencyclidine) on the behavior of the animals. Of the three schedules, the FR (20) key press proved to be impractical as a behavioral model for ischemia. The other two schedules have not been examined to the same extent, but these pilot studies indicate them to be more sensitive, and hence more effective as models, in measuring the ischemic insult on the rats. Under these two schedules of reinforcement, phencyclidine (PCP), was shown to assist in the recovery of behavioral function.