Mohammed A K, Wahlström G, Archer T, Nordberg A
Department of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
J Neural Transm Park Dis Dement Sect. 1990;2(4):285-94. doi: 10.1007/BF02252923.
Physostigmine and tetrahydroaminoacridine (THA) have been reported to improve cognitive function in patients with Alzheimer's disease. Two experiments were conducted to examine the effects of these anticholinesterase agents on learning in aged rats pretreated chronically with barbital. In the first experiment animals received barbital in their drinking water for 46 weeks. Controls were given only water. On days 100-104 of abstinence, when the animals were 20 months old, acquisition of the Morris maze task was initiated after treatment with physostigmine. It was found that physostigmine improved learning of the maze task in control but not barbital treated rats. In the second experiment animals received barbital solution or water as in experiment one. On days 100-103 of abstinence they were injected with THA before being tested in the Morris water maze. It was found that THA improved learning in both barbital treated and control rats. These results corroborate clinical findings of improved cognitive function following treatment with THA, and suggest that the therapeutic effects of THA may be mediated by mechanisms distinct from cholinesterase inhibition. Furthermore chronic barbital treatment could be used as a model to study cognitive disturbances in experimental animals.
据报道，毒扁豆碱和四氢氨基吖啶（THA）可改善阿尔茨海默病患者的认知功能。进行了两项实验，以研究这些抗胆碱酯酶药物对长期用巴比妥预处理的老年大鼠学习能力的影响。在第一个实验中，动物在饮用水中摄入巴比妥46周。对照组只给予水。在戒断的第100 - 104天，当动物20个月大时，在用毒扁豆碱治疗后开始进行莫里斯水迷宫任务的训练。发现毒扁豆碱改善了对照组大鼠的迷宫任务学习能力，但对用巴比妥处理的大鼠没有作用。在第二个实验中，动物如实验一中那样接受巴比妥溶液或水。在戒断的第100 - 103天，它们在莫里斯水迷宫中接受测试前被注射了THA。发现THA改善了用巴比妥处理的大鼠和对照组大鼠的学习能力。这些结果证实了用THA治疗后认知功能改善的临床发现，并表明THA的治疗作用可能由不同于胆碱酯酶抑制的机制介导。此外，慢性巴比妥治疗可作为研究实验动物认知障碍的模型。
