Effect of a novel TRH analogue, JTP-2942, on impairment of passive avoidance and water maze tasks in rats with permanent middle cerebral artery occlusion

We investigated the effects of JTP-2942, a novel TRH analogue, on the performance of passive avoidance and water maze tasks in rats with chronic middle cerebral artery (MCA) occlusion. Male Wistar rats (9 weeks old and weighing about 300 g) were subjected to MCA occlusion. JTP-2942 (0.3, 1.0, or 3.0 mg/kg) was orally administered once a day for 9 weeks from one week after MCA occlusion. The compound was administered just after the cognitive function trials. Seven weeks after MCA occlusion, the retention trial of the passive avoidance task was performed at 24 hr after the acquisition trial. MCA-occluded rats showed significant impairment of retention latency when compared with sham-operated rats, and JTP-2942 (1.0 and 3.0 mg/kg) improved the passive avoidance retention latency. Fourteen consecutive acquisition trials of the water maze task (one per day), were performed from eight weeks after MCA occlusion. MCA-occluded rats showed significant impairment of acquisition when compared with sham-operated rats. Administration of JTP-2942 (3.0 mg/kg) improved spatial recognition escape latency and length of the swimming path to the hidden underwater platform in the MCA-occluded rats. The present results indicate that JTP-2942 has an antiamnesic effect, and also improves spatial recognition, suggesting that it may be a useful therapeutic agent for patients with dementia.