Stemmelin J, Cassel J C, Will B, Kelche C
Laboratoire de Neurosciences Comportementales et Cognitives, UMR 7521 ULP/CNRS, Strasbourg, France.
Behav Brain Res. 1999 Jan;98(1):53-66. doi: 10.1016/s0166-4328(98)00052-7.
As a first step, the present experiment aimed at characterizing learning and memory capabilities, as well as some motor and sensorimotor faculties, in aged (24-26.5 months) Long-Evans female rats. As a second step, a psychopharmacological approach was undertaken in order to examine the sensitivity of aged rats to muscarinic blockade and to cholinomimetic treatments. Young adult (3-5.5 months) and aged rats were tested for beam-walking performance, locomotor activity in the home cage and an open field, and spatial learning/memory performance in a water maze and a radial maze. Spontaneous alternation rates were assessed in a T-maze. Statistical analysis discriminated between aged rats showing moderate impairment (AMI) and those showing severe impairment (ASI) in the water maze test. Beside their different degrees of impairment in the water maze, AMI and ASI rats were similarly (no significant difference) impaired in beam-walking capabilities, home cage activity and radial maze performance. In the spontaneous alternation task aged rats were not impaired and, in the open-field test, AMI rats were hypoactive, but not as much as ASI rats. Neither of the cognitive deficits was correlated with a locomotor or a sensorimotor variable, or with the body weight. When tested in the radial maze, a low dose of scopolamine (0.1 mg/kg i.p.) produced memory impairments which were significant in AMI and ASI rats, but not in young rats. Combined injections of scopolamine and physostigmine (0.05 and 0.1 mg/kg) or tacrine (THA, 3 mg/kg) showed physostigmine (0.1 mg/kg) to compensate for the scopolamine-induced impairments only in AMI rats. whereas THA was efficient in both AMI and ASI rats. The results indicate: (i) that rats with different degrees of spatial memory impairment in the water maze are similarly hypersensitive to muscarinic blockade when tested in a radial maze test; and (ii) that under the influence of a dose of scopolamine which is subamnesic in young rats, aged rats respond to anticholinesterase treatments according to the level of performance achieved in the water maze: moderately impaired rats are sensitive to both physostigmine and THA, whereas more severely impaired rats are sensitive only to THA.
作为第一步，本实验旨在表征老年（24 - 26.5个月）的Long - Evans雌性大鼠的学习和记忆能力，以及一些运动和感觉运动能力。作为第二步，采用心理药理学方法来研究老年大鼠对毒蕈碱阻断和拟胆碱治疗的敏感性。对年轻成年（3 - 5.5个月）和老年大鼠进行了横梁行走性能、在饲养笼和旷场中的运动活动以及在水迷宫和放射状迷宫中的空间学习/记忆性能测试。在T迷宫中评估自发交替率。统计分析区分了在水迷宫测试中表现出中度损伤（AMI）和重度损伤（ASI）的老年大鼠。除了在水迷宫中的不同损伤程度外，AMI和ASI大鼠在横梁行走能力、饲养笼活动和放射状迷宫性能方面同样受损（无显著差异）。在自发交替任务中，老年大鼠未受损，在旷场测试中，AMI大鼠活动不足，但不如ASI大鼠明显。两种认知缺陷均与运动或感觉运动变量或体重无关。在放射状迷宫中测试时，低剂量东莨菪碱（0.1 mg/kg腹腔注射）产生的记忆损伤在AMI和ASI大鼠中显著，但在年轻大鼠中不显著。联合注射东莨菪碱和毒扁豆碱（0.05和0.1 mg/kg）或他克林（THA，3 mg/kg）显示，毒扁豆碱（0.1 mg/kg）仅在AMI大鼠中能补偿东莨菪碱诱导的损伤。而THA在AMI和ASI大鼠中均有效。结果表明：（i）在水迷宫中具有不同程度空间记忆损伤的大鼠在放射状迷宫测试中对毒蕈碱阻断同样高度敏感；（ii）在年轻大鼠中产生亚遗忘剂量的东莨菪碱影响下，老年大鼠根据在水迷宫中达到的表现水平对抗胆碱酯酶治疗作出反应：中度受损的大鼠对毒扁豆碱和THA均敏感，而受损更严重的大鼠仅对THA敏感。
