Grigoryan G A, Mitchell S N, Hodges H, Sinden J D, Gray J A
Department of Psychology, Institute of Psychiatry, DeCrespigny Park, London, UK.
Pharmacol Biochem Behav. 1994 Nov;49(3):511-21. doi: 10.1016/0091-3057(94)90063-9.
Experiments were conducted to test the hypothesis that the enhancing effect of nicotine on water maze performance in rats with lesions of the forebrain cholinergic projection systems (FCPS) is mediated by an interaction with the noradrenergic system, in particular the ascending dorsal noradrenergic bundle (DNAB) and its projection areas. Three groups of rats received lesions of either: i) the nucleus basalis (NBM) and medial septal area/diagonal band (MSA/DB) by infusion of alpha-amino-3-hydroxy-4-izoxazole propionic acid (AMPA) (FCPS group), ii) DNAB, by infusion of 6-hydroxydopamine (6-OHDA) (NOR group), or iii) both FCPS plus DNAB (COMB group). Control animals received vehicle. Choline acetyltransferase activity was reduced in the cortex and hippocampus of the FCPS and COMB groups and in the hippocampus of the NOR group. NA level was reduced in the cortex and hippocampus of the FCPS and COMB groups, but not the FCPS group. In a reference memory task, the performance of both the NOR and COMB groups, but not the NOR group, was significantly worse than that of controls; there was no effect of nicotine administration (0.1 mg/kg) on escape latency or other measures in this task. In a working memory task, FCPS and COMB rats took longer to find the submerged platform on the second and following trials, and there was a significant enhancement of performance by nicotine in both groups, but not in controls. These results indicate that the enhancing effects of nicotine in rats with FCPS lesions are not mediated by an interaction with the DNAB.
尼古丁对前脑胆碱能投射系统（FCPS）损伤大鼠水迷宫表现的增强作用是通过与去甲肾上腺素能系统相互作用介导的，特别是上行背侧去甲肾上腺素能束（DNAB）及其投射区域。三组大鼠分别接受以下损伤：i）通过注入α-氨基-3-羟基-4-异恶唑丙酸（AMPA）损伤基底核（NBM）和内侧隔区/斜角带（MSA/DB）（FCPS组），ii）通过注入6-羟基多巴胺（6-OHDA）损伤DNAB（NOR组），或iii）同时损伤FCPS和DNAB（COMB组）。对照动物接受溶剂。FCPS组和COMB组的皮质和海马以及NOR组的海马中的胆碱乙酰转移酶活性降低。FCPS组和COMB组的皮质和海马中的去甲肾上腺素（NA）水平降低，但FCPS组未降低。在参考记忆任务中，NOR组和COMB组的表现均明显差于对照组，但FCPS组无差异；在此任务中，给予尼古丁（0.1mg/kg）对逃避潜伏期或其他指标无影响。在工作记忆任务中，FCPS组和COMB组的大鼠在第二次及后续试验中找到水下平台的时间更长，尼古丁使两组的表现均显著提高，但对照组未提高。这些结果表明，尼古丁对FCPS损伤大鼠的增强作用不是通过与DNAB相互作用介导的。
