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

开发针对老年大鼠昼夜节律和预期行为损伤的有效药物。

• 批准号: 03671098
• 负责人: SHIBATA Shigenobu
• 金额: $ 1.34万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03671098/
• 关键词: Ciycadian Rhythm; Suprachiasmatic; Sleep-activity Rhythm; Cognition; Anticipation; Animal model; Acetylcholine; Cognitive enhancer; 向精神薬; 体内時計; サ-カディアンリズム; 夜間徘廻; 抗痴呆薬; 精神分裂病; タンパク合成阻害薬; 神経伝達物質

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".

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。

项目成果

Shigenobu Shibata: "NSF-Tokyo Symposium on Biological Timing 「Involvement of NMDA receptor mechaniom in the regulation of circadian clock fanction of the suprachiasmatic nucleus in vitro」" Elsevier., 5 (1993)

Shigenobu Shibata：“NSF-东京生物计时研讨会“NMDA 受体机制参与体外视交叉上核生物钟功能的调节””Elsevier., 5 (1993)

Shigenobu Shibata,Atsuko Tsuneyoshi,Toshiyuki Hamada,Keiko Tominaga and Shigenori Watanabe: "Phase-resetting effect of 8-OH-DPAT,a serotoninlA receptor agonist,on the circadian rhythm of firing rate in the rat suprachiasmatic nuclei in vitro." Brain Res.

Shigenobu Shibata、Atsuko Tsuneyoshi、Toshiyuki Hamada、Keiko Tominaga 和 Shigenori Watanabe：“5-羟色胺1A 受体激动剂 8-OH-DPAT 对体外大鼠视交叉上核放电率昼夜节律的相位重置作用。”

R.Aguilar-Roblero,R.,S.Shibata,J.C.Speh,R.Drucker-Colin and R.Y.Moore: "Morphological and functional development of the suprachiasmatic nucleus in transplanted fetal hypothalamus." Brain Res. 580. 288-296 (1992)

R.Aguilar-Roblero、R.、S.Shibata、J.C.Speh、R.Drucker-Colin 和 R.Y.Moore：“移植胎儿下丘脑视交叉上核的形态和功能发育”。

Keiko Tominaga,Shigenobu Shibata,Showa Ueki and Shigenori Watanabe: "Effects of 5-HT1A receptor agonists on the circadian rhythm of wheel-running activity in hamsters." Eur.J.Pharmacology. 214. 79-84 (1992)

Keiko Tominaga、Shigenobu Shibata、Showa Ueki 和 Shigenori Watanabe：“5-HT1A 受体激动剂对仓鼠轮跑活动昼夜节律的影响”。

K.Tominaga,S.Shibata S.Ueki,S.Watanabe: "Effects of inhibitory and excitatory drugs on the metabolic rhythm of hamster suprachiasmatie nucleus in vitro." European Journal of pharmacology.

K.Tominaga，S.Shibata S.Ueki，S.Watanabe：“抑制性和兴奋性药物对仓鼠视交叉上核体外代谢节律的影响”。