Ragozzino M E, Gold P E
Department of Psychology, University of Virginia, Charlottesville 22903, USA.
Neuroscience. 1995 Oct;68(4):981-8. doi: 10.1016/0306-4522(95)00204-v.
Morphine infusions into the medial septum produce memory deficits which can be attenuated by concurrent intraseptal injections of glucose. The mnemonic deficits following intraseptal morphine injections may be due, in part, to opioid inhibition of cholinergic neurons projecting to the hippocampus, with glucose reducing the effect. The present experiment determined whether glucose injections into the medial septum attenuate the effects of intraseptal morphine injections on hippocampal acetylcholine release and on memory. Samples of extracellular acetylcholine levels were assessed at 12 min intervals using in vitro microdialysis with high-performance liquid chromatography with electrochemical detection. Intraseptal morphine injections (4.0 nmol) reduced acetylcholine output starting at 12 min and lasting up to 72 min post-injection. Glucose (18.3 nmol) injected concomitantly with morphine reversed the drug infusions in the septum 20 min prior to spontaneous alternation testing. Intraseptal morphine infusions reduced alternation scores; this behavioral effect was reversed by concurrent glucose infusions. The effect of drugs infused into the septal area on spontaneous alternation performance and acetylcholine output were positively correlated. These findings suggest that memory deficits induced by intraseptal morphine injections may result, at least partially, from a decrease in the activity of cholinergic neurons and that this effect is reversed by glucose.
向内侧隔区注射吗啡会导致记忆缺陷，而同时向隔区内注射葡萄糖可减轻这种缺陷。隔区内注射吗啡后出现的记忆缺陷，部分可能是由于阿片类物质抑制了投射至海马体的胆碱能神经元，而葡萄糖可减轻这种作用。本实验旨在确定向内侧隔区注射葡萄糖是否能减轻隔区内注射吗啡对海马体乙酰胆碱释放及记忆的影响。使用高效液相色谱-电化学检测的体外微透析技术，每隔12分钟评估一次细胞外乙酰胆碱水平样本。隔区内注射吗啡（4.0纳摩尔）会使乙酰胆碱输出量从注射后12分钟开始降低，并持续至注射后72分钟。在自发交替测试前20分钟，与吗啡同时注射的葡萄糖（18.3纳摩尔）可逆转隔区内的药物输注。隔区内注射吗啡会降低交替得分；同时注射葡萄糖可逆转这种行为效应。注入隔区的药物对自发交替表现和乙酰胆碱输出的影响呈正相关。这些发现表明，隔区内注射吗啡引起的记忆缺陷可能至少部分是由于胆碱能神经元活性降低所致，而葡萄糖可逆转这种效应。
