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

视交叉上核（SCN）被认为是哺乳动物昼夜节律的起搏器。谷氨酸，P物质，NPY和GABA在光信息从视网膜传递到SCN的过程中起着重要作用，因此我们研究了它们是否能重置SCN神经元活动的昼夜节律。在黑暗条件下，它们能产生类似于黑暗诱导的时相变化，而NPY和GABA受体激动剂蝇蕈类则能产生类似于黑暗诱导的时相变化，如果在一天中的固定时间内只进食一餐，它们会在几天内表现出对进食时间的预期活动，这种预期活动在禁食几天后仍保持在其通常的时相位置。目前，食物耐受节律所需的物理基础尚不清楚。这种食物耐受节律的预期活动受到衰老和NMDA受体拮抗剂MK 801的损害。这种预期活动的损害可通过胆碱能药物槟榔碱和认知增强剂bifemelane的共同治疗得到改善。这些结果表明，预期行为缺陷可能是一种有用的“社会夹带”缺陷模型。

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".