EVIDENCE FOR HISTAMINERGIC AROUSAL MECHANISMS IN THE HYPOTHALAMUS OF CAT
EVIDENCE FOR HISTAMINERGIC AROUSAL MECHANISMS IN THE HYPOTHALAMUS OF CAT
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DOI：
10.1016/0028-3908(88)90159-1
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发表时间：
1988-02-01
影响因子：
4.7
通讯作者：
JOUVET, M
中科院分区：
文献类型：
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作者：
LIN, JS;SAKAI, K;JOUVET, M
为了检查全身和局部注射各种组胺能和抗组胺能药物对睡眠-觉醒周期的影响，对25只成年猫进行了23小时的测谎记录。-Fluroromethylhistidine (.alpha。以20 mg/kg剂量腹腔注射组氨酸脱羧酶特异性抑制剂-FMH，可显著增加深慢波睡眠（S2）和减少清醒(W)，而不改变光慢波睡眠（S1）和矛盾睡眠（PS）。腹腔注射mepyramine (1mg和5mg /kg)，一种众所周知的组胺h1受体拮抗剂，增加深慢波睡眠，减少清醒，以及矛盾睡眠。双侧注射α。-FMH （50 .mu）.mu g / 1。L)进入下丘脑后腹外侧，在那里最近发现了组胺免疫反应神经元，导致清醒显著减少，深度慢波睡眠增加。同样，注射甲皮拉米(120 .mu。.mu g / 1。L)在相同的结构中引起清醒的显著减少，以及深慢波和矛盾睡眠的增加。相比之下，局部注射SKF-91488 (50 .mu。.mu g / 1。l)，一种特定的组胺- n -甲基转移酶抑制剂，导致清醒程度显著增加，慢波睡眠（SWS）和矛盾睡眠（paradoxical sleep）的觉醒程度显著降低。注射组胺，剂量分别为5、30和60。g / l .mu。L，也有剂量依赖性地增加觉醒和减少慢波睡眠，而这些作用被甲皮拉米预处理完全阻断。结果表明，下丘脑的组胺能系统在觉醒机制中起重要作用，其作用是通过h1受体介导的。
Polygraphic 23-hr recordings were carried out in 25 adult cats in order to examine the effects of both systemic and local injections of various histaminergic and antihistaminergic drugs on sleep-waking cycles. .alpha.-Fluroromethylhistidine (.alpha.-FMH), a specific inhibitor of histidine decarboxylase, when injected intraperitoneally at a dose of 20 mg/kg, induced a significant increase in deep slow wave sleep (S2) and a decrease in wakefulness (W), without modifying light slow wave sleep (S1) and paradoxical sleep (PS). Intraperitoneal injections of mepyramine (1 mg and 5 mg/kg), a well-known histamine H1-receptor antagonist, increased deep slow wave sleep and decreased wakefulness, as well as paradoxical sleep. Bilateral injections of .alpha.-FMH (50 .mu.g/1 .mu.l) into the ventrolateral posterior hypothalamus, where histamine immunoreactive neurones have been recently identified, resulted in a significant decrease in wakefulness and increase in deep slow wave sleep. Similarly, injections of mepyramine (120 .mu.g/1 .mu.l) in the same structures caused a significant decrease in wakefulness and an increase in deep slow wave and paradoxical sleep as well. In contrast, local injections of SKF-91488 (50 .mu.g/1 .mu.l), a specific inhibitor of histamine-N-methyltransferase, led to a significant increase in wakefulness and decrease in both slow wave sleep (SWS) and paradoxical sleep. Injections of histamine, at doses of 5, 30 and 60 .mu.g/l .mu.l, also increased wakefulness and decreased slow wave sleep dose dependently, while these effects were completely blocked by pretreatment with mepyramine. The results suggest that histaminergic systems in the hypothalamus play an important role in arousal mechanisms and their actions are mediated through H1-receptors.