Arendt T, Allen Y, Marchbanks R M, Schugens M M, Sinden J, Lantos P L, Gray J A
Department of Biochemistry, Institute of Psychiatry, London, U.K.
Neuroscience. 1989;33(3):435-62. doi: 10.1016/0306-4522(89)90397-7.
Oral administration of ethanol (20% v/v) to male Sprague-Dawley rats for different periods of time up to 28 weeks resulted in profound reductions of acetylcholine content, in vitro synthesis and release of acetylcholine, choline uptake, activities of choline acetyltransferase, acetylcholinesterase and pyruvate decarboxylase, content of noradrenaline, serotonin and, to a lesser extent, dopamine throughout the brain. Changes were fully and partially reversible by a 4 weeks' ethanol-free period following a treatment of 8 and 18 weeks, respectively. They remained persistent, however, after 28 weeks of treatment. Performance in an eight arm-radial maze revealed a severe impairment in both spatial and non-spatial reference and working memory. A similar pattern of memory impairment was obtained after ibotenate lesion of the cholinergic basal forebrain projection system. In order to test whether this memory impairment depends on cholinergic deafferentation of the cortex, cholinergic-rich fetal basal forebrain cell suspensions were transplanted into cortex, hippocampus or both these sites in ethanol treated rats. Cholinergic-rich transplants, but not cholinergic-poor transplants, were effective in ameliorating impaired memory function and measures of cholinergic activity in the basal forebrain projection system. The behavioural efficacy of the basal forebrain grafts was well correlated with measures of both transplant volume and the degree to which they restored acetylcholine content at the transplant site; these transplants had no effect, however, on brain monoamine levels. The effects of the cholinergic-rich transplants into cortical and hippocampal sites were additive in their amelioration of performance in the radial maze. Similarly, ibotenate lesions of the sites of origin of the cholinergic projections to neocortex (in the region of the nucleus basalis magnocellularis) and hippocampus (the medial septal areas and nucleus of the diagonal band), respectively, were additive in their deleterious effects on maze performance. There were no qualitative differences in the susceptibility of the four different types of memory performance measured (spatial and non-spatial reference and working memory) to the effects of ethanol, ibotenate lesions of the cholinergic projection system, or cholinergic-rich brain tissue transplants. Thus, overall, the results indicate that the forebrain cholinergic system acts as a whole, without major functional differences between the projections originating in the medial septal area/diagonal band complex and the basal nucleus, and that it discharges a very general function in cognitive processes.(ABSTRACT TRUNCATED AT 400 WORDS)
给雄性斯普拉格 - 道利大鼠口服20%（v/v）乙醇，持续不同时间段直至28周，结果导致全脑乙酰胆碱含量、乙酰胆碱的体外合成与释放、胆碱摄取、胆碱乙酰转移酶、乙酰胆碱酯酶和丙酮酸脱羧酶的活性、去甲肾上腺素、5-羟色胺以及程度较轻的多巴胺含量大幅降低。在分别经过8周和18周的乙醇处理后，给予4周的无乙醇期，这些变化分别完全或部分可逆。然而，在28周的处理后，这些变化仍然持续存在。八臂放射状迷宫实验中的表现显示，空间和非空间参考及工作记忆均严重受损。胆碱能基底前脑投射系统经鹅膏蕈氨酸损伤后，也出现了类似的记忆损伤模式。为了测试这种记忆损伤是否取决于皮质的胆碱能传入缺失，将富含胆碱能的胎儿基底前脑细胞悬液移植到乙醇处理大鼠的皮质、海马或这两个部位。富含胆碱能的移植组织而非胆碱能缺乏的移植组织，能有效改善记忆功能受损以及基底前脑投射系统中胆碱能活性的指标。基底前脑移植组织的行为学效应与移植体积以及它们恢复移植部位乙酰胆碱含量的程度密切相关；然而，这些移植组织对脑单胺水平没有影响。将富含胆碱能的移植组织分别植入皮质和海马部位，对放射状迷宫实验表现的改善作用具有累加性。同样，分别对胆碱能投射至新皮质（大细胞基底核区域）和海马（内侧隔区和斜角带核）的起源部位进行鹅膏蕈氨酸损伤，对迷宫实验表现的有害影响也具有累加性。所测量的四种不同类型记忆表现（空间和非空间参考及工作记忆）对乙醇、胆碱能投射系统的鹅膏蕈氨酸损伤或富含胆碱能的脑组织移植的影响，在易感性方面没有质的差异。因此，总体而言，结果表明前脑胆碱能系统作为一个整体发挥作用，起源于内侧隔区/斜角带复合体和基底核的投射之间没有主要的功能差异，并且它在认知过程中发挥着非常普遍的功能。（摘要截断于400字）
