DIFFERENTIATING ANALGESIC AND NON-ANALGESIC DRUG ACTIVITIES ON RAT HOT PLATE - EFFECT OF BEHAVIORAL END-POINT
DIFFERENTIATING ANALGESIC AND NON-ANALGESIC DRUG ACTIVITIES ON RAT HOT PLATE - EFFECT OF BEHAVIORAL END-POINT
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DOI：
10.1016/0304-3959(91)90207-e
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发表时间：
1991-11-01
期刊：
影响因子：
7.4
通讯作者：
CARTER, RB
中科院分区：
文献类型：
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作者：
CARTER, RB
评估了行为终点对在55 ℃大鼠热板程序中获得的结果的贡献。具体而言，将仅后爪舔终点的使用与后爪舔或跳终点的使用进行比较。在每种条件下测定原型镇痛和非镇痛化合物对反应潜伏期增加的影响。尽管吗啡、羟考酮和可待因在每种条件下的作用相似，但许多非镇痛剂的作用根据所用终点而显著不同。氯氮平，氯丙嗪，硫利达嗪，阿托品，东莨菪碱，苯那替嗪，育亨宾，咪唑克生和赛庚啶产生剂量依赖性的增加反应潜伏期下，后爪舔只条件下，但没有增加lavonin时，后爪舔或跳终点使用。氟哌啶醇、舒必利、苯扎托品、甲基阿托品、酚妥拉明、哌唑嗪、甲硫替平、麦角新碱、苯海拉明、帕吉林和地西泮在仅舔后爪的条件下不能增加反应延迟。此外，而地西泮，氯丙嗪，戊巴比妥，丹曲林和乙醇产生剂量依赖性增加成功的空中翻正所需的高度，增加后爪舔或跳lavonium只发生在近麻醉剂量的戊巴比妥和乙醇。这些数据表明，后爪舔舐终点易受外源性药理学活性的干扰。发挥毒蕈碱胆碱能和α 2-肾上腺素能拮抗剂作用的药物特别能够破坏这种行为。干扰与任何其他药理作用无关，尽管其他活动可能干扰反应。相比之下，后爪舔或跳终点不能检测骨骼肌松弛活性，并且仅在使用接近麻醉剂量的药物时检测到粗大运动损伤。目前的数据表明，通过大鼠热板检测非镇痛药物活性可以通过使用后爪舔或跳终点来最小化。
The contribution of behavioral endpoint to results obtained in the 55-degrees-C rat hot plate procedure was assessed. Specifically, the use of a hind paw lick-only endpoint was compared to that of a hind paw lick-or-jump endpoint. Effects of prototypical analgesic and non-analgesic compounds on response latency increases were determined under each condition. Whereas the effects of morphine, oxycodone and codeine were similar under each condition, effects of a number of non-analgesic agents differed markedly depending upon the endpoint used. Clozapine, chlorpromazine, thioridazine, atropine, scopolamine, benactyzine, yohimbine, idazoxan and cyproheptadine produced dose-dependent increases in response latency under the hind paw lick-only condition but did not increase latencies when the hind paw lick-or-jump endpoint was used. Haloperidol, sulpiride, benztropine, methyl atropine, phentolamine, prazosin, methiothepin, methysergide, diphenhydramine, pargyline and diazepam failed to increase response latencies under the hind paw lick-only condition. Moreover, whereas diazepam, chlorpromazine, pentobarbital, dantrolene and ethanol produced dose-dependent increases in the height required for successful aerial righting, increases in hind paw lick-or-jump latencies occurred only following near-anesthetic doses of pentobarbital and ethanol. These data indicate that the hind paw lick endpoint is susceptible to perturbation by extraneous pharmacologic activities. Drugs exerting muscarinic cholinergic and alpha2-adrenergic antagonist effects are particularly able to disrupt this behavior. Disruption is not associated specifically with any other pharmacologic action, although other activities may interfere with the response. In contrast, the hind paw lick-or-jump endpoint fails to detect skeletal muscle relaxant activity and only detects gross motor impairment when near-anesthetic doses of drugs are used. The present data suggest that detection of non-analgesic drug activities by rat hot plate can be minimized by use of a hind paw lick-or-jump endpoint.