Dumas Julie A, Saykin Andrew J, McDonald Brenna C, McAllister Thomas W, Hynes Mary L, Newhouse Paul A
Department of Psychiatry, Clinical Neuroscience Research Unit, University of Vermont College of Medicine, Burlington, VT 05401, USA.
Am J Geriatr Psychiatry. 2008 Apr;16(4):272-82. doi: 10.1097/JGP.0b013e3181602a2b.
An important aspect of furthering our understanding of the central nervous system function after menopause is to examine the cerebral circuitry that appears to be influenced by cholinergic antagonist drugs in the presence and absence of estrogen. This pilot study investigated the effects of two anticholinergic drugs on brain activation and working memory performance in postmenopausal women not taking estrogen. This approach simulates the effects of age- or disease-related neuroreceptor or neuronal loss by temporarily blocking pre- and postsynaptic muscarinic and nicotinic cholinergic receptors.
Six healthy postmenopausal women took part in three drug challenges using the antinicotinic drug mecamylamine (MECA, 20 mg, oral), the antimuscarinic drug scopolamine (SCOP, 2.5 microg/kg, i.v.), and placebo during functional magnetic resonance imaging. The cognitive measure was a visually presented verbal N-back test of working memory.
Neither MECA nor SCOP significantly impaired performance on the verbal N-back. Functional magnetic resonance imaging results showed greater increases in frontal lobe activation in the placebo condition relative to each drug condition with different specific regional activation for MECA and SCOP.
These preliminary results suggest that brain activation patterns are sensitive to cholinergic modulation in postmenopausal women and that differential effects may be observed following nicotinic versus muscarinic blockade. This approach offers a potentially valuable method for modeling age-related changes in brain function, and the findings may have implications for cholinergic contributions to normal and pathologic aging.
进一步了解绝经后中枢神经系统功能的一个重要方面是研究在有或没有雌激素的情况下，似乎受胆碱能拮抗剂药物影响的脑回路。这项初步研究调查了两种抗胆碱能药物对未服用雌激素的绝经后女性大脑激活和工作记忆表现的影响。这种方法通过暂时阻断突触前和突触后毒蕈碱能和烟碱能胆碱能受体，模拟与年龄或疾病相关的神经受体或神经元丧失的影响。
六名健康的绝经后女性在功能磁共振成像期间，使用抗烟碱药物美加明（MECA，20毫克，口服）、抗毒蕈碱药物东莨菪碱（SCOP，2.5微克/千克，静脉注射）和安慰剂进行了三次药物激发试验。认知测量是对工作记忆进行视觉呈现的言语n-back测试。
MECA和SCOP均未显著损害言语n-back测试的表现。功能磁共振成像结果显示，与每种药物条件相比，安慰剂条件下额叶激活的增加更大，MECA和SCOP有不同的特定区域激活。
这些初步结果表明，绝经后女性的大脑激活模式对胆碱能调节敏感，并且在烟碱阻断和毒蕈碱阻断后可能观察到不同的效应。这种方法为模拟与年龄相关的脑功能变化提供了一种潜在有价值的方法，研究结果可能对胆碱能在正常和病理性衰老中的作用有影响。
