Kitchen I, McDowell J
Toxicol Lett. 1985 Aug;26(2-3):101-5. doi: 10.1016/0378-4274(85)90152-3.
The development of ketocyclazocine antinociception has been measured in lead-exposed rats as an indirect determinant of kappa-opioid receptor system development. Perinatal lead administration (at 300 and 1000 ppm) in the maternal drinking water from conception to weaning, impaired the antinociceptive activity of ketocyclazocine (using the paw pressure test) in 10-day-old rats. Lead caused a dose-dependent impairment of ketocyclazocine antinociception, the paw pressure threshold for 0.4 mg/kg being reduced from 207 g to 135 g in the 1000 ppm lead dose-group. Ketocyclazocine antinociception was impaired in the high-lead dose-group at 21 days, but unaffected at 30 days. Blood lead levels in 10-day-old animals were below 35 micrograms/100 ml in the low-lead dose-group and below 50 micrograms/100 ml in the high-lead dose-group. It is suggested that lead may disrupt the development of kappa-opioid receptor systems in the central nervous system and that this disruption occurs early in development.
已在铅暴露大鼠中测量了酮环唑新的抗伤害感受作用，以此作为κ-阿片受体系统发育的间接决定因素。从受孕到断奶期间，在母鼠饮用水中添加围产期铅（浓度为300 ppm和1000 ppm），会损害10日龄大鼠中酮环唑新的抗伤害感受活性（采用爪压痛试验）。铅会导致酮环唑新抗伤害感受作用出现剂量依赖性损害，在1000 ppm铅剂量组中，0.4 mg/kg的爪压痛阈值从207 g降至135 g。高铅剂量组在21日龄时酮环唑新的抗伤害感受作用受损，但在30日龄时未受影响。低铅剂量组10日龄动物的血铅水平低于35微克/100毫升，高铅剂量组低于50微克/100毫升。研究表明，铅可能会扰乱中枢神经系统中κ-阿片受体系统的发育，且这种扰乱发生在发育早期。
