EVALUATION OF NEUROPROTECTION AND BEHAVIORAL RECOVERY BY THE KAPPA-OPIOID, PD117302 FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA

The effects of the selective kappa-opioid, PD117302 ((+/-)-trans-N-met yl-N-2-(1-pyrrolidinyl) cyclohexyl benzo bthiophene-4-acetamide), on transient (15 min) global forebrain ischemia, induced by four-vesse l occlusion, was evaluated using a multiple fixed-ratio, fixed-interva l schedule of food presentation in rats. The schedule produced distinc tive patterns of responding in the fixed-ratio and fixed-interval comp onents. Ischemia produced CA1 hippocampal necrosis and prolonged suppr ession of responding under both schedule components. When responding r esumed, the pattern of responding rapidly returned. Response disruptio n and CA1 hippocampal necrosis were minimal or nonexistent in sham-occ luded rats. Behavioral recovery time under both components of the sche dule of reinforcement correlated with CA1 necrosis. On average, CA1 ne crosis was less, and behavioral recovery time was shorter, in rats tre ated with PD117302 postocclusion as compared with vehicle-treated rats . The difference, however, did not reach statistical significance. The se results demonstrate the utility of schedule-controlled responding f or evaluating potentially therapeutic compounds for the treatment of i schemic injury. These results also further characterize the neuroprote ctive actions of kappa opioids.