Suh H W, Song D K, Kim Y H, Choi Y S, Yoo J S, Tseng L F
Department of Pharmacology, Hallym University, Kangwon-Do, S. Korea.
Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;352(6):614-9. doi: 10.1007/BF00171319.
The present study was designed to investigate the modulatory effects of stimulation of GABAA and GABAB receptors at supraspinal sites on antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. The effects of the GABAA and GABAB receptor agonists, muscimol and baclofen respectively, on the antinociception induced by morphine (a mu-receptor agonist), beta-endorphin (an epsilon-receptor agonist), D-Pen2,5-enkephalin (DPDPE, a delta-receptor agonist) and U50,488H ([trans-3,4-dichloroN-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeocetamide]; a kappa-receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed using the tail-flick and hot-plate tests. Muscimol at doses of 25-200 ng, administered i.c.v. alone did not affect the latencies of tail-flick and hot-plate thresholds, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by i.c.v. administered morphine (2 micrograms), beta-endorphin (1 microgram), DPDPE (10 micrograms), and U50,488H (60 micrograms). Baclofen (1.25-10 ng) administered i.c.v. alone did not affect the latencies of the tail-flick and hot-plate responses, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by beta-endorphin and U50,488H, without affecting morphine- or DPDPE-induced responses. Our results indicate that activation of GABAA receptors at the supraspinal sites by i.c.v. injection of muscimol antagonizes antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. On the other hand, activation of GABAB receptors at supraspinal sites by i.c.v. baclofen antagonizes antinociception induced by i.c.v. administered epsilon- and kappa-opioid agonists, but not mu- or delta-opioid agonists.
本研究旨在探讨脊髓上部位刺激GABAA和GABAB受体对脊髓上给予μ、ε、δ和κ阿片受体激动剂诱导的抗伤害感受的调节作用。分别研究了GABAA和GABAB受体激动剂蝇蕈醇和巴氯芬对脑室内注射吗啡（一种μ受体激动剂）、β-内啡肽（一种ε受体激动剂）、D- Pen2,5-脑啡肽（DPDPE，一种δ受体激动剂）和U50,488H（[反式-3,4-二氯-N-甲基-N-[2-(1-吡咯烷基)环己基]苯乙酰胺]；一种κ受体激动剂）诱导的抗伤害感受的影响。使用甩尾和热板试验测定抗伤害感受。单独脑室内注射剂量为25 - 200 ng的蝇蕈醇不影响甩尾潜伏期和热板阈值，但剂量依赖性地减弱了脑室内注射吗啡（2微克）、β-内啡肽（1微克）、DPDPE（10微克）和U50,488H（60微克）诱导的甩尾和热板反应抑制。单独脑室内注射巴氯芬（1.25 - 10 ng）不影响甩尾和热板反应潜伏期，但剂量依赖性地减弱了β-内啡肽和U50,488H诱导的甩尾和热板反应抑制，而不影响吗啡或DPDPE诱导的反应。我们的结果表明，脑室内注射蝇蕈醇激活脊髓上部位的GABAA受体可拮抗脊髓上给予μ、ε、δ和κ阿片受体激动剂诱导的抗伤害感受。另一方面，脑室内注射巴氯芬激活脊髓上部位的GABAB受体可拮抗脑室内给予ε和κ阿片激动剂诱导的抗伤害感受，但不拮抗μ或δ阿片激动剂诱导的抗伤害感受。
