Riekkinen P, Aaltonen M, Sirviö J, Riekkinen P
Department of Pathology, University of Kuopio, Finland.
Physiol Behav. 1991 Jun;49(6):1147-52. doi: 10.1016/0031-9384(91)90342-l.
This study examined the effects of tetrahydroaminoacridine (THA, an anticholinesterase) on water-maze (WM) spatial reference (stable platform location during training) and spatial working memory (reversal of platform location) learning in young intact/medial septal (MS)-lesioned and aged rats. THA (1 or 3 mg/kg, IP) had no effect on reference or working memory performance of young intact rats. MS lesions decreased cholineacetyltransferase activity in the hippocampus and also impaired spatial reference and working memory. THA at 3 mg/kg stabilized MS lesion-induced reference memory performance deficit (path length increase), but was ineffective at 1 mg/kg. THA had no effect on the working memory performance of MS-lesioned rats. Aged rats were impaired in spatial reference and working memory tasks. THA at 3 mg/kg partially stabilized the age-induced spatial reference memory deficits, but was ineffective at 1 mg/kg. THA at either 1 or 3 mg/kg did not alleviate the age-related deficit in the working memory version of WM. The present results suggest that some of the age-related WM deficits may be related to the degeneration of the MS-hippocampus cholinergic system and that THA may be effective in stabilizing the reference memory deficits induced by hippocampal cholinergic dysfunction.
本研究考察了四氢氨基吖啶（THA，一种抗胆碱酯酶药物）对年轻未受损/内侧隔区（MS）损伤大鼠以及老年大鼠在水迷宫（WM）空间参考记忆（训练期间平台位置稳定）和空间工作记忆（平台位置反转）学习中的影响。THA（1或3毫克/千克，腹腔注射）对年轻未受损大鼠的参考记忆或工作记忆表现没有影响。MS损伤降低了海马中的胆碱乙酰转移酶活性，也损害了空间参考记忆和工作记忆。3毫克/千克的THA稳定了MS损伤诱导的参考记忆表现缺陷（路径长度增加），但1毫克/千克时无效。THA对MS损伤大鼠的工作记忆表现没有影响。老年大鼠在空间参考记忆和工作记忆任务中受损。3毫克/千克的THA部分稳定了年龄诱导的空间参考记忆缺陷，但1毫克/千克时无效。1或3毫克/千克的THA均未减轻WM工作记忆版本中与年龄相关的缺陷。目前的结果表明，一些与年龄相关的WM缺陷可能与MS - 海马胆碱能系统的退化有关，并且THA可能有效地稳定由海马胆碱能功能障碍诱导的参考记忆缺陷。
