Murphy A Z, Murphy R M, Zemlan F P
Department of Physiology, University of Cincinnati College of Medicine, OH 45267-0559.
Psychopharmacology (Berl). 1992;108(1-2):123-30. doi: 10.1007/BF02245296.
The ability of 5-HT1A and 5-HT1B agonists to alter a spinal animal's nociceptive threshold was examined using two analgesiometric tests. In the spinal withdrawal reflex test, administration of the selective 5-HT1A agonists ipsapirone, gepirone and PAPP resulted in significant dose-dependent increases in receptive field (RF) area for withdrawal reflexes when compared to predrug baseline values, indicating an increase in nociceptive sensitivity. The average overall percent maximal increase in RF area following administration of 5-HT1A selective compounds was: 80 +/- 16% for the ventroflexion reflex, 90 +/- 6% for the dorsiflexion reflex and 87 +/- 8% for the lateral flexion reflex. Similar to the effects noted with 5-HT1A agonists, administration of 5-HT1B agonists RU24969, mCPP and TFMPP resulted in a hyperalgesic response with an overall percent maximal increase of 43 +/- 6% for the ventroflexion reflex, 51 +/- 6% for the dorsiflexion reflex and 38 +/- 9% for the lateral flexion reflex. In the tail-flick analgesiometric test, administration of the 5-HT1A agonists 8-OH-DPAT and ipsapirone and the 5-HT1B agonists RU24969 and mCPP resulted in a significant dose-dependent increase in tail-flick latencies when compared to predrug baseline values, indicating a decrease in nociceptive sensitivity to noxious thermal stimuli. No differences in magnitude of the effect of the two receptor subtypes were found, indicating that stimulation of either 5-HT1A or 5-HT1B receptors was equipotent in producing the antinociceptive tail-flick response.(ABSTRACT TRUNCATED AT 250 WORDS)
使用两种痛觉测定试验,研究了5-羟色胺1A(5-HT1A)和5-羟色胺1B(5-HT1B)激动剂改变脊髓动物痛觉阈值的能力。在脊髓退缩反射试验中,与给药前的基线值相比,给予选择性5-HT1A激动剂伊沙匹隆、吉哌隆和PAPP后,退缩反射的感受野(RF)面积出现显著的剂量依赖性增加,表明痛觉敏感性增强。给予5-HT1A选择性化合物后,RF面积平均最大总体增加百分比为:腹屈反射80±16%,背屈反射90±6%,侧屈反射87±8%。与5-HT1A激动剂的作用类似,给予5-HT1B激动剂RU24969、mCPP和TFMPP后出现痛觉过敏反应,腹屈反射最大总体增加百分比为43±6%,背屈反射为51±6%,侧屈反射为38±9%。在甩尾痛觉测定试验中,与给药前的基线值相比,给予5-HT1A激动剂8-羟基二丙胺基四氢萘(8-OH-DPAT)和伊沙匹隆以及5-HT1B激动剂RU24969和mCPP后,甩尾潜伏期出现显著的剂量依赖性增加,表明对有害热刺激的痛觉敏感性降低。未发现两种受体亚型的作用强度存在差异,表明刺激5-HT1A或5-HT1B受体在产生抗伤害性甩尾反应方面具有同等效力。(摘要截短为250字)