Evaluation of Neuroprotection and Behavioral Recovery by the Kappa- Opioid, PD 117302 Following Transient Forebrain Ischemia
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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The effects of selective kappa-opioid, PD117302 --trans-N- methyl-N-2--1-pyrrolidinylcyclohexyl benzothiophene-4-acetamide, on transient 15 min global forebrain ischemia, induced by four-vessel occlusion, was evaluated using a multiple fixed-ratio, fixed-interval schedule of food presentation in rats. The schedule produced distinctive patterns of responding in the fixed-ratio and fixed-interval components. Ischemia produced CA1 hippocampal necrosis and prolonged suppression of responding under both schedule components. When responding resumed, the pattern of responding rapidly returned. Response disruption and CA1 hippocampal necrosis were minimal or nonexistent in sham-occluded rats. Behavioral recovery time under both components of the schedule of reinforcement correlated with CA1 necrosis. On average, CA1 necrosis was less, and behavioral recovery time was shorter in rats treated with PD117302 post-occlusion as compared with vehicle-treated rats. The difference, however, did not reach statistical significance. These results demonstrate the utility of schedule-controlled responding for evaluating potentially therapeutic compounds for the treatment of ischemic injury. These results also further characterize the neuroprotective actions of kappa opioids. Ischemia, Operant behavior, Kappa opioid, Rat.
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