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通过下丘脑内微量注射L-5-羟色氨酸逆转对氯苯丙氨酸诱导的失眠

Reversibility of para-chlorophenylalanine-induced insomnia by intrahypothalamic microinjection of L-5-hydroxytryptophan.

作者信息

Denoyer M, Sallanon M, Kitahama K, Aubert C, Jouvet M

机构信息

Département de Médecine Expérimentale, INSERM U52, CNRS UA1195, Faculté de Médecine, Université Claude Bernard, Lyon, France.

出版信息

Neuroscience. 1989;28(1):83-94. doi: 10.1016/0306-4522(89)90234-0.

DOI:10.1016/0306-4522(89)90234-0
PMID:2527339
Abstract

Para-chlorophenylalanine, a blocker of serotonin biosynthesis by inhibiting tryptophan hydroxylase, induced total insomnia which was accompanied in cat by a permanent discharge of ponto-geniculo-occipital activity. L-5-Hydroxytryptophan microinjection (1-4 micrograms/0.5 microliters) in the anterior hypothalamus 72 h after para-chlorophenylalanine administration, restored both slow wave sleep and paradoxical sleep with variable latencies for each state of sleep. On the contrary, ponto-geniculo-occipital activity was never suppressed. The hypnogenic effects of L-5-hydroxytryptophan were always followed by a return of the para-chlorophenylalanine-induced insomnia. On the other hand, the temperature recording did not show any alteration of the cerebral temperature after para-chlorophenylalanine treatment but the subsequent L-5-hydroxytryptophan microinjection was followed by hyperthermia. Using immunohistochemistry for serotonin after intrahypothalamic L-5-hydroxytryptophan microinjection in parachlorophenylalanine-pretreated cat, we defined a restricted region of the anterior hypothalamus possibly responsible for the hypnogenic effect. This region included the lateral hypothalamus and the anterior hypothalamic area. It is suggested that the reversible hypersomnia after L-5-hydroxytryptophan microinjection in the anterior hypothalamus in para-chlorophenylalanine-pretreated cat is due to a neurohormonal action of serotonin: serotonin could act upon the anterior hypothalamus which secondarily inhibits a waking system located in the ventrolateral hypothalamus leading to the appearance of paradoxical sleep.

摘要

对氯苯丙氨酸是一种通过抑制色氨酸羟化酶来阻断血清素生物合成的物质,它会导致完全失眠,在猫身上伴有脑桥-膝状体-枕叶活动的持续放电。在给予对氯苯丙氨酸72小时后,向下丘脑前部微量注射L-5-羟色氨酸(1-4微克/0.5微升),可恢复慢波睡眠和异相睡眠,每种睡眠状态的潜伏期各不相同。相反,脑桥-膝状体-枕叶活动从未被抑制。L-5-羟色氨酸的催眠作用总是伴随着对氯苯丙氨酸诱导的失眠的复发。另一方面,体温记录显示对氯苯丙氨酸治疗后脑温没有任何变化,但随后微量注射L-5-羟色氨酸后会出现体温过高。在经对氯苯丙氨酸预处理的猫下丘脑内微量注射L-5-羟色氨酸后,使用血清素免疫组织化学方法,我们确定了下丘脑前部一个可能与催眠作用有关的受限区域。该区域包括下丘脑外侧区和下丘脑前区。有人提出,在经对氯苯丙氨酸预处理的猫下丘脑前部微量注射L-5-羟色氨酸后出现的可逆性失眠是由于血清素的神经激素作用:血清素可能作用于下丘脑前部,进而抑制位于下丘脑腹外侧的觉醒系统,导致异相睡眠的出现。

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