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神经降压素、促甲状腺激素释放激素及δ-阿片受体拮抗剂ICI 174864对大鼠酒精诱导麻醉的影响。

The effect of neurotensin, TRH and the delta-opioid receptor antagonist ICI 174864 on alcohol-induced narcosis in rats.

作者信息

Widdowson P S

机构信息

Anglo-European College of Chiropractic, Bournemouth, Dorset, U.K.

出版信息

Brain Res. 1987 Oct 27;424(2):281-9. doi: 10.1016/0006-8993(87)91472-7.

DOI:10.1016/0006-8993(87)91472-7
PMID:2823997
Abstract

The effects of microinjections of thyrotropin-releasing hormone (TRH), neurotensin and ICI 174864 into the nucleus accumbens, nucleus caudatus, septum and mesencephalic periaqueductal grey were studied on ethanol-induced narcosis in the rat. Levels of narcosis were assessed by alterations in ethanol-induced hypothermia and sleep time. Ethanol produces a 2 degree C fall in body temperature over the first hour which then recovered over the next 2 h. Sedation was produced to the extent that the righting reflex was lost for between 80 and 90 min. In the nucleus caudatus all 3 peptides were ineffective at altering narcosis. In the periaqueductal grey, septum and accumbens, TRH (5 micrograms) and ICI 174864 (1 microgram) microinjections significantly reduced the sleep time by between 50 and 70%. ICI 174864 was approximately 10 times more potent that TRH at reducing the sleep time. In addition, both these peptides significantly accelerated the recovery from the ethanol-induced hypothermia in the periaqueductal grey, septum and accumbens. ICI 174864 prevented the ethanol-induced fall in body temperature. Neurotensin (5 micrograms) significantly increased the sleep time by up to 50% and potentiated the ethanol-induced hypothermia. These results suggest that the administration of TRH or the blockade of delta-opioid receptors, resulting in an inhibition of endogenous enkephalin transmission, may significantly inhibit ethanol narcosis in the rat. Opposing this, the application of neurotensin appears to potentiate ethanol narcosis. These results also indicate that endogenous enkephalin release plays an important role in ethanol narcosis.

摘要

研究了向大鼠伏隔核、尾状核、隔区和中脑导水管周围灰质微量注射促甲状腺激素释放激素(TRH)、神经降压素和ICI 174864对乙醇诱导麻醉的影响。通过乙醇诱导的体温过低和睡眠时间的变化来评估麻醉水平。乙醇在最初1小时内使体温下降2摄氏度,随后在接下来的2小时内恢复。产生的镇静作用使翻正反射丧失80至90分钟。在尾状核中,所有3种肽对改变麻醉均无效。在导水管周围灰质、隔区和伏隔核中,注射TRH(5微克)和ICI 174864(1微克)可使睡眠时间显著减少50%至70%。在减少睡眠时间方面,ICI 174864的效力约为TRH的10倍。此外,这两种肽均显著加速了导水管周围灰质、隔区和伏隔核中乙醇诱导的体温过低的恢复。ICI 174864可防止乙醇诱导的体温下降。神经降压素(5微克)可使睡眠时间显著增加多达50%,并增强乙醇诱导的体温过低。这些结果表明,给予TRH或阻断δ-阿片受体,导致内源性脑啡肽传递受到抑制,可能会显著抑制大鼠的乙醇麻醉。与此相反,应用神经降压素似乎会增强乙醇麻醉。这些结果还表明,内源性脑啡肽释放在乙醇麻醉中起重要作用。

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