Effects of thyrotropin-releasing hormone on behavioral disturbances in middle cerebral artery-occluded rats

The effects of thyrotropin releasing hormone (TRH) on behavioral and histological changes were studied in rats subjected to left middle cerebral artery occlusion. The drug was given i.p. once or several times a day from 1 week after occlusion for 2 weeks. A single administration of TRH (1 and 10 mg/kg) did not affect the neurological deficits, but recovery of the deficits was accelerated by multiple administration (7 times a day) of TRH and single administration (once a day) of YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), a new TRH analogue with a longer half-life. Both YM-14673 and single (1 and 10 mg/kg) and multiple administration of TRH ameliorated the disturbance of passive avoidance learning. Neuronal degeneration in the cerebral cortex and striatum was not influenced by the administration of TRH. Thus, we found that neurological deficits and disturbance of passive avoidance learning behavior in middle cerebral artery-occluded rats could be ameliorated by administration of TRH.