Dilsaver S C, Majchrzak M J
Department of Psychiatry, University of Michigan, Ann Arbor 48109.
Life Sci. 1987 Dec 14;41(24):2607-14. doi: 10.1016/0024-3205(87)90274-8.
Supersensitivity of a muscarinic mechanism is implicated in the pathophysiology of depression. Bright artificial light is efficacious in the treatment of Seasonal Affective Disorder (SAD). We studied the effect of constant bright light (11,500 lux) on the sensitivity of adult, male rats to oxotremorine, 1.5 mg/kg ip, using a repeated measures design. Oxotremorine challenges were proceeded by the injection of methylscopolamine, 1 mg/kg ip, by 30 minutes. Temperature was telemetrically measured every 10 minutes for 120 minutes starting 10 minutes after the injection of oxotremorine. Prior to and after 7 continuous days of exposure to bright light, the sample exhibited a hypothermic response of 2.50 +/- 0.48 degrees C (mean +/- SEM) and 0.29 +/- 0.31 degrees C (mean +/- SEM), respectively (p less than 0.0014). All 7 animals exhibited blunting to the thermic response to oxotremorine. Bright light also blocked the capacity of amitriptyline to supersensitize a central muscarinic mechanism. Exposure to light at an intensity of 300 lux for 7 days had no effect on the thermic response to oxotremorine. These data are consistent with the hypotheses that the biology of depression involves supersensitivity of central muscarinic mechanisms and that the effects of bright artificial light are not the consequence of shifting circadian rhythms.
毒蕈碱机制的超敏反应与抑郁症的病理生理学有关。明亮的人造光对季节性情感障碍（SAD）的治疗有效。我们采用重复测量设计，研究了持续明亮光照（11,500勒克斯）对成年雄性大鼠对1.5毫克/千克腹腔注射氧化震颤素敏感性的影响。在注射氧化震颤素前30分钟，腹腔注射1毫克/千克甲基东莨菪碱后进行氧化震颤素激发试验。从注射氧化震颤素后10分钟开始，每10分钟进行一次体温遥测，持续120分钟。在连续7天暴露于明亮光照之前和之后，样本分别表现出2.50 +/- 0.48摄氏度（平均值 +/- 标准误）和0.29 +/- 0.31摄氏度（平均值 +/- 标准误）的低温反应（p小于0.0014）。所有7只动物对氧化震颤素的热反应均出现钝化。明亮光照还阻断了阿米替林使中枢毒蕈碱机制超敏的能力。暴露于300勒克斯强度的光照7天对氧化震颤素的热反应没有影响。这些数据与以下假设一致：抑郁症的生物学机制涉及中枢毒蕈碱机制的超敏反应，并且明亮人造光的作用不是昼夜节律改变的结果。
