The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines.
The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines.
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小鼠甩尾试验中测量的麻醉药及其拮抗剂的抗伤害活性与脑儿茶酚胺合成增加之间的相关性。
DOI：
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发表时间：
1976
影响因子：
3.5
通讯作者：
K. K. Brosius
中科院分区：
文献类型：
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作者：
A. Bloom;W. Dewey;L. Harris;K. K. Brosius
研究了几种麻醉性药物、麻醉性拮抗剂-镇痛剂和麻醉性拮抗剂对小鼠脑内多巴胺和去甲肾上腺素合成的影响，并与它们在甩尾实验中的活性有关。通过测定注射~3H-酪氨酸形成的~3H-多巴胺和~3H-去甲肾上腺素的积累量来估测儿茶酚胺的合成。吗啡引起甩尾活动和儿茶酚胺合成的剂量相关增加。每种麻醉性镇痛剂在皮下注射抗伤害性剂量(ED80)30分钟后产生明显的儿茶酚胺合成增加。在相同的条件下，甩尾试验中不活跃的药物，如五唑碱，会减少儿茶酚胺的合成和环氮唑碱的合成；纳洛酮和纳曲酮则没有明显的作用。然而，在甩尾试验中不活跃且不改变给药后30分钟儿茶酚胺合成的环氮唑辛，在给药2分钟后表现出甩尾活动并增加了儿茶酚胺的合成。给药2分钟后，吗啡两种活性均消失。同样，在给予在甩尾试验中有效的吗啡剂量(10 mg/kg)并在30分钟时增加儿茶酚胺合成后2小时，既没有观察到甩尾活动，也没有增加儿茶酚胺合成。纳洛酮阻断了吗啡和美沙酮的抗伤害性作用和增加的儿茶酚胺合成。这些研究的结果表明，类麻醉剂药物的甩尾活性与它们促进儿茶酚胺合成的能力之间存在相关性。这些数据支持这样一种假设，即脑儿茶酚胺可能参与了麻醉性止痛剂的甩尾反应和其他行为的中枢调节。
The effects of several narcotics, narcotic antagonists-analgesics and narcotic antagonists on the synthesis of dopamine and norepinephrine in mouse brain were estimated and related to their activity in the tail-flick test. Catecholamine synthesis was estimated by measuring the accumulation of 3H-dopamine and 3H-norepinephrine formed from an injection of 3H-tyrosine. Morphine produced dose-related increases in both tail-flick activity and catecholamine synthesis. Each of the narcotic analgesics produced a significant increase in catecholamine synthesis 30 minutes after the subcutaneous injection of an antinociceptive dose (ED80). Under these same conditions, drugs which are inactive in the tail-flick test, such as pentazocine, produced a decrease in catecholamine synthesis and cyclazocine; naloxone and naltrexone were without significant effect. However, cyclazocine, which was inactive in the tail-flick test and did not alter catecholamine synthesis 30 minutes after administration, demonstrated tail-flick activity and produced increased catecholamine synthesis 2 minutes after its administration. Morphine was devoid of either activity 2 minutes after administration. Similarly, at 2 hours after the administration of a dose of morphine (10 mg/kg) that was active in the tail-flick test and increased catecholamine synthesis at 30 minutes, neither tail-flick activity nor increased catecholamine synthesis was observed. Naloxone blocked both the antinociceptive action and the increased catecholamine synthesis produced by both morphine and methadone. The results of these studies indicate that a correlation exists between tail-flick activity of narcotic-like drugs and their ability to increase catecholamine synthesis. These data support the hypothesis that brain catecholamines may be involved in the central mediation of the tail-flick response and other actions of the narcotic analgesics.