Sleep deprivation in the rat: An animal model of mania
Sleep deprivation in the rat: An animal model of mania
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DOI：
10.1016/0924-977x(95)00023-i
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发表时间：
1995-01-01
影响因子：
5.6
通讯作者：
Fratta, W
中科院分区：
文献类型：
--
作者：
Gessa, GL;Pani, L;Fratta, W
本实验室已广泛研究了平台法睡眠剥夺大鼠模型作为一种可能的躁狂症动物模型。在睡眠剥夺期结束时，大鼠在回到其笼舍后并没有立即入睡，而是显示出约30分钟的清醒期，在此期间，动物呈现出似乎模仿特发性躁狂症中存在的症状的一组症状。特别是，在此期间，动物表现出失眠、高度多动、易怒、攻击性、性欲亢进和刻板。氟哌啶醇（0.2 mg/kg）可有效缩短睡眠潜伏期，而L-舒必利则弱得多（< 50 mg/kg）。多巴胺D-1受体拮抗剂SCH 23390在缩短睡眠潜伏期方面表现出极高的效力和功效，在3 μ g/kg剂量下观察到显著效果。特异性D-1受体激动剂SKF 38393的给药显著延长了失眠伴相关行为综合征的时间。当在饮食中加入锂并在睡眠剥夺期间摄入足量的锂以产生0.7-1.0 mEq/l的血清锂水平时，睡眠潜伏期和自发活动显著减少。纳洛酮（1-10 mg/kg）给药以剂量相关方式缩短睡眠潜伏期。相比之下，吗啡（1和5 mg/kg，i. p.），β-内啡肽和[D-Ala（2），D-Leu（5）]脑啡肽（i. c. v.，2 μ g和1 μ g）明显延长失眠时间。该模型不仅证实了大鼠的睡眠丧失通常先于并可能引发人类的躁狂发作，而且表明阿片类药物-多巴胺相互作用可能在躁狂症中发挥致病作用。
The model of sleep deprivation in rats by the platform method has been extensively studied in our laboratory as a possible animal model of mania. At the end of the period of sleep deprivation, the rat does not fall asleep as soon as it is returned to its home cage, but shows a period of wakefulness of about 30 min, during which the animal presents a cohort of symptoms that appear to mimic those present in idiopathic mania. In particular, during this period the animal displays insomnia, a high degree of hyperactivity, irritability, aggressiveness, hypersexuality and stereotypy. Haloperidol (0.2 mg/kg) was effective in reducing latency to sleep, while L-sulpiride was much weaker (< 50 mg/kg). The dopamine D-1 receptor antagonist SCH 23390 exhibited an extremely high potency and efficacy in reducing sleep latency, a significant effect being observed with 3 mu g/kg. The administration of the specific D-1 receptor agonist SKF 38393 markedly prolonged the period of insomnia with the correlated behavioral syndrome. When lithium was added to the diet and consumed during the sleep deprivation period in adequate amounts to produce serum lithium levels of 0.7-1.0 mEq/l, sleep latency and locomotor activity were significantly reduced. The administration of naloxone (1-10 mg/kg) reduced the latency to sleep in a dose-related manner. By contrast, morphine (1 and 5 mg/kg, i.p.), beta-endorphin and [D-Ala(2),D-Leu(5)]enkephalin (i.c.v., 2 and 1 mu g, respectively) markedly prolonged the insomnia. The model not only represents a confirmation in the rat that sleep loss often precedes and may trigger a manic episode in man, but suggests that an opioid-dopamine interaction may play a pathogenetic role in mania.