Ying S W, Rusak B, Delagrange P, Mocaer E, Renard P, Guardiola-Lemaitre B
Department of Psychology, Dalhousie University, Halifax, Nova Scotia, Canada.
Eur J Pharmacol. 1996 Jan 18;296(1):33-42. doi: 10.1016/0014-2999(95)00684-2.
We studied the effects of drugs related to melatonin on neuronal firing activity in the suprachiasmatic nucleus, intergeniculate leaflet and other brain areas in urethane-anesthetized Syrian hamsters. We tested melatonin and two naphthalenic derivatives of melatonin, a putative agonist (S20098: N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide), and a putative antagonist (S20928: N-[2-(1-naphthyl)ethyl]cyclobutyl carboxamide). Both melatonin and S20098 given intraperitoneally (i.p.) were able to suppress firing rates of cells in a similar dose-dependent manner, but the effects of S20098 were longer lasting. Iontophoresis of melatonin dose dependently depressed spontaneous and light-evoked activity of cells in the suprachiasmatic nucleus and intergeniculate leaflet, while iontophoresis of S20098 was relatively ineffective, probably because it is a poorly charged compound. S20928 (2.0-10 mg/kg, i.p.) alone decreased firing rates of light-sensitive cells by 25-50% for 5-30 min in the suprachiasmatic nucleus and intergeniculate leaflet; however, low doses (< 2.0 mg/kg) of S20928 partially blocked the effects of melatonin agonists on most cells. The non-selective serotonin antagonist metergoline did not block the effects of either melatonin agonist. Both melatonin agonists and antagonists were less effective when applied to cells in the hippocampus and dorsal lateral geniculate nucleus. These results indicate that S20098 is an agonist acting probably on melatonin receptors in the Syrian hamster brain. S20928 may have mixed agonist/antagonist properties, but at low doses appears to function as an antagonist at melatonin receptors in the suprachiasmatic nucleus and intergeniculate leaflet.
我们研究了与褪黑素相关的药物对氨基甲酸乙酯麻醉的叙利亚仓鼠视交叉上核、膝间小叶及其他脑区神经元放电活动的影响。我们测试了褪黑素及其两种萘衍生物，一种假定的激动剂（S20098：N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺）和一种假定的拮抗剂（S20928：N-[2-(1-萘基)乙基]环丁基甲酰胺）。腹腔注射（i.p.）褪黑素和S20098均能以相似的剂量依赖性方式抑制细胞放电率，但S20098的作用持续时间更长。褪黑素离子导入以剂量依赖性方式抑制视交叉上核和膝间小叶细胞的自发活动和光诱发活动，而S20098离子导入相对无效，可能是因为它是一种电荷较少的化合物。单独使用S20928（2.0 - 10 mg/kg，i.p.）可使视交叉上核和膝间小叶中光敏感细胞的放电率在5 - 30分钟内降低25 - 50%；然而，低剂量（< 2.0 mg/kg）的S20928可部分阻断褪黑素激动剂对大多数细胞的作用。非选择性5-羟色胺拮抗剂美替拉酮不阻断任何一种褪黑素激动剂的作用。当应用于海马体和背外侧膝状核中的细胞时，褪黑素激动剂和拮抗剂的效果均较差。这些结果表明，S20098可能是一种作用于叙利亚仓鼠脑中褪黑素受体的激动剂。S20928可能具有混合的激动剂/拮抗剂特性，但在低剂量时似乎在视交叉上核和膝间小叶中作为褪黑素受体的拮抗剂起作用。
