Muhammad B Y, Kitchen I
Receptors and Cellular Regulation Research Group, School of Biological Sciences, University of Surrey, Guildford, UK.
Pharmacol Biochem Behav. 1994 Apr;47(4):927-33. doi: 10.1016/0091-3057(94)90298-4.
The use and abuse of benzodiazepines is widespread and we have begun to address whether maternal exposure to these drugs influences the development of opioid systems. We have studied the effect of maternal diazepam treatment on stress-induced antinociception in the neonatal offspring. Diazepam (1 or 10 mg/kg) was administered twice daily to mothers from conception. Pre- and postweanling rat pups were assessed for opioid-mediated stress-induced antinociception by 3-min swimming and measuring nociception using the tail immersion test. In preweanling rats there was stress-induced antinociception in both vehicle- and diazepam-treated animals but in diazepam-treated groups (1 and 10 mg/kg) this was insensitive to reversal by the opioid antagonist naloxone, suggesting that nonopioid systems are operating this response. In postweanling rats a similar insensitivity to naloxone was observed in 1 mg/kg diazepam-treated groups; with 10 mg/kg diazepam there was no significant antinociception. The results suggest that maternal diazepam treatment interferes with the development of stress-mediated responses and that part of this toxicity is due to actions on opioid systems in the CNS.
苯二氮䓬类药物的使用和滥用十分普遍，我们已经开始研究母亲接触这些药物是否会影响阿片系统的发育。我们研究了母亲使用地西泮治疗对新生后代应激诱导的抗伤害感受的影响。从受孕开始，每天给母亲两次注射地西泮（1或10毫克/千克）。通过3分钟游泳试验评估断奶前和断奶后的幼鼠阿片介导的应激诱导的抗伤害感受，并使用尾浸试验测量伤害感受。在断奶前的大鼠中，溶剂对照组和地西泮治疗组的动物均出现应激诱导的抗伤害感受，但在地西泮治疗组（1和10毫克/千克）中，这种反应对阿片拮抗剂纳洛酮的逆转不敏感，这表明非阿片系统在起作用。在断奶后的大鼠中，1毫克/千克地西泮治疗组对纳洛酮也有类似的不敏感性；10毫克/千克地西泮组则没有明显的抗伤害感受。结果表明，母亲使用地西泮治疗会干扰应激介导反应的发育，这种毒性部分归因于对中枢神经系统阿片系统的作用。
