Development of effective drugs on impairments of Circardian rhythms and anticipatory behaivior in old rats.

点击翻译按钮获取中文摘要

The suprachiasmatic nucleus(SCN)has been identified as a pacemaker for mammalian circadian rhythms.Glutamate,substance P,NPY and GABA have been found to play an important role in the transmission of light information from retina to SCN.Therefore we investigated whether these chemicals can reset the phase of the circadian rhythms of SCN neuron activity.NMDA as glutamate receptor agonist and substance P produced phase changes similar to light-induced phase changes,while NPY and muscimolas a GABA receptor agonist produced those similar to dark-induced phase changes.If food is restricted to single meal scheduled at fixed time in the day,they will within a few days,exhibit a locomotor activity which anticipates mealtime.The anticipatory activity persists at its usual phase position when food is withheld for several days. At present,physical substrates necessary for food-entrainable rhythms are uncertain.This food-anticipatory activity was impaired by aging and a treatment with MK801,NMDA receptor antagonist.The impairment of this anticipatory activity was improved by the cotreatment with arecoline a cholinergic drug and bifemelane,a cognitive enhancer.These results suggest that deficit of anticipatory behavior may be a useful model of a deficit of "social entrainment".