茶碱改善东莨菪碱诱发的大鼠记忆障碍

金宗濂 文镜 王卫平 贺闻涛

摘 要:   用高效液相色谱测定了不同年龄SD大鼠与记忆有关脑区的腺苷和乙酰胆碱水平。结果表明, 18~20月龄鼠的脑内腺苷含量明显高于3~6月龄鼠, 而乙酰胆碱(ACh)含量却显著低于3~6月龄鼠。经腹腔给大鼠注射东莨宕碱建立近期记忆障碍模型, 同时经脑室给予茶碱后, 其跳台成绩明显优于对照组, 且脑内ACh含量亦显著升高。提示腺苷含量的随龄增加可能是老年记忆障碍的一个重要因素, 茶碱作为腺苷受体阻断剂可能通过提高脑内ACh水平起到改善东莨宕碱诱发的大鼠记忆障碍的作用, 因此茶碱可能是治疗老年记忆障碍的一种有希望的药物。
关键词: 腺苷; 茶碱; 乙酰胆碱; 东莨宕碱; 老年学习记忆障碍
学科分类号: Q427

The role of theophylline in the improvement of scop-induced
learning and memory impairment

JIN Zong-Lian WEN Jing WANG Wei-Ping HE Wen-Tao
(College of Applied Sciences and Humanities of Beijing Union University, Beijing 100083)

Abstract:   Adenosine and ACh contents in hippocampus, striatum region around the nucleus of basal meynert (NBM) and the frontal and temporal parts of rat cortex were measured by a high performance liquid chromotography-electronic detector (HPLC-ECD). Adenosine content in 1820 month-old rats was significantly higher than that of 36 month-old rats, while ACh content in 1820 month-old rats was lower than that of 36 month-old ones. Learning and memory impairment models were established by induction of SD rats with scopolamine (0.5 mg/kg, ip), which were injected with an adenosine recepter antagonist theophylline (1.0 mg/5 μl, icv), and the step-down test was performed. The error frequency in the step-down test decreased significantly (P<0.05), and the retention time was longer than that of control. Furthermore, ACh content increased in all the three different brain regions. The above results suggest that adenosine may play an important role in senile learning and memory impairment, and theophylline may improve scopolamine-induced learning and memory impairment by increasing ACh content. In consequence, theophylline could be a promising drug for ameliorating senile learning and memory impairment.
Key words: adenosine; theophylline; acetylcholine; scopolamine; senile learning and memory impairment

Supported by the Natural Science Foundation of Beijing (No.5932007)

Corresponding author. Tel: 86-10-62004522; Fax: 86-10-62388927; E-mail: biology@china2.ygi.edu.cn 390 

金宗濂(北京联合大学应用文理学院, 北京 100083)
文镜(北京联合大学应用文理学院, 北京 100083)
王卫平(北京联合大学应用文理学院, 北京 100083)
贺闻涛(北京联合大学应用文理学院, 北京 100083)

参 考 文 献

 [1] Smith CJ, Perry EK, Perry RH et al. Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders. J Neurochem, 1988, 50: 847~856.
 [2] Ikeda Y, Edlund A. Evidence for cholinergic M receptors decreasing in aging SD rat brain. J Trans, 1990, 30: 25~32.
 [3] Jin ZL, Lee TF, Zhou SJ et al. Age-dependent change in the inhibitory effect of an adenosine agonist on hippocampal acetylcholine release in rats. Brain Res Bulle, 1993, 30: 149~152.
 [4] Jackson EK, Ohnishi A. Development and application of a simple microassay for adenosine in rat plasma. Hypertension, 1987, 10 (2): 189~197.
 [5] Gamberini G, Ferioli V, Zanoli P et al. A high-performance liquid chromatographic method for the analysis of adenosine and some metabolites in the brain tissue of rats. Chromatography, 1992, 34 (11~12): 563~567.
 [6] Niklas T.  Improvement in the separation and detection of ACh and Ch using HPLC and electrochemical detection. J Chromato, 1990, 502: 337~349.
 [7] Ma XF (马晓峰), Ye WL (叶惟泠), Mei ZT (梅镇彤). Comparative study on cholinergic transmission in frontal cortex of aged and young rats. J Neuroanat (神经解剖学杂志), 2000, 16 (1): 1~6 (in Chinese with English abstract).
 [8] Everitt BJ. The effect of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on the acquisition and retention of a conditional visual discrimination implications for cholinergic hypotheses of learning and memory. Neuroscience, 1987, 22: 441.
 [9] Wang S (王 绍). Relationship of neurotransmitters. Acta Bethune Med Sci Univ (白求恩医科大学学报), 1986, 12: 5 (in Chinese with English abstract).
[10] Jin ZL (金宗濂), Wang WP (王卫平), Zhao H (赵 红). Relationship of adenosine with senile dementia of Alzheimer′s type. Proc Psychol (心理学动态), 1995, 4: 4~7 (in Chinese with English abstract).

  Received 2000-01-17  Accepted 2000-04-13