Dornan W A, McCampbell A R, Tinkler G P, Hickman L J, Bannon A W, Decker M W, Gunther K L
Department of Psychology, Illinois Wesleyan University, Bloomington 61701, USA.
Behav Brain Res. 1996 Dec;82(1):93-101. doi: 10.1016/s0166-4328(97)81112-6.
In this study, we investigated the effects of 192 IgG saporin injections into the medial septal area (MSA), or nucleus basalis magnocellularis (NBM), and combined injections into the MSA and NBM, on water maze and radial arm maze performance in the male rat. The results of the present study reveal a dissociation between the effects of 192 IgG saporin injections into the basal forebrain on the performance of two tasks of spatial learning in the rat. Bilateral injections of 192 IgG saporin into the NBM, MSA or combined MSA/NBM failed to disrupt water maze performance when compared to controls. In contrast, injections of 192 IgG saporin into the MSA, NBM or MSA/NBM induced mild impairments on a radial arm maze task. Overall, the disruption of spatial learning observed in this study was, however, relatively mild compared to deficits in spatial learning reported using less selective lesions of the cholinergic basal forebrain. Consequently, the results of this study suggest that a selective reduction in cholinergic transmission in the basal forebrain is, by itself, insufficient to account for the functional impairments observed in spatial learning in the rat. Although our data do support the use of 192 IgG saporin as a selective cholinergic toxin in the basal forebrain, they further suggests that assessment of spatial learning in the rat following 192 IgG saporin lesions of the basal forebrain in combination with lesions to other neurotransmitter systems, may be a more viable approach to the elucidation of the neuropathological mechanisms that are associated with the cognitive deficits seen in Alzheimer's disease.
在本研究中,我们调查了向雄性大鼠内侧隔区(MSA)、大细胞基底核(NBM)注射192 IgG皂草素,以及向MSA和NBM联合注射,对水迷宫和放射状臂迷宫表现的影响。本研究结果揭示了向基底前脑注射192 IgG皂草素对大鼠两项空间学习任务表现的影响之间存在分离。与对照组相比,向NBM、MSA或联合MSA/NBM双侧注射192 IgG皂草素并未破坏水迷宫表现。相比之下,向MSA、NBM或MSA/NBM注射192 IgG皂草素会在放射状臂迷宫任务中引起轻度损伤。然而,与使用对胆碱能基底前脑选择性较低的损伤所报道的空间学习缺陷相比,本研究中观察到的空间学习破坏相对较轻。因此,本研究结果表明,基底前脑中胆碱能传递的选择性减少本身不足以解释在大鼠空间学习中观察到的功能损伤。虽然我们的数据确实支持将192 IgG皂草素用作基底前脑中的选择性胆碱能毒素,但它们进一步表明,在192 IgG皂草素损伤基底前脑后结合对其他神经递质系统的损伤来评估大鼠的空间学习,可能是阐明与阿尔茨海默病中所见认知缺陷相关的神经病理机制的更可行方法。