Zmitrovich A C, Brake S C, Liu P Y, Hamowy A S, Hutchings D E
New York State Psychiatric Institute, Department of Developmental, Psychobiology, New York 10032.
Neurotoxicol Teratol. 1994 May-Jun;16(3):251-5. doi: 10.1016/0892-0362(94)90046-9.
Two doses of methadone were administered by osmotic minipump from Day 8 of gestation through parturition, a dosing technique previously shown to produce physical dependence in the dams. A pair-fed control group received sterile water via minipump and was allowed to eat and drink only the amount consumed by the high-dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. The effects of methadone on maternal and offspring toxicity replicated our previous findings. At 29-31 days of age each treated and control animal was tested either for changes in acoustic startle amplitude or the rest-activity cycle. Methadone treated offspring were no different from the controls on either measure. These findings support the hypothesis derived from our earlier research that prenatal exposure to methadone produces a prolonged but transitory opioid abstinence. This is evidenced by increased startle amplitude and a disturbed rest-activity cycle that peaks at approximately 3 weeks of age. We demonstrate that these effects are no longer evident at 4 weeks of age. Together, these findings define a state of hyperexcitability in the young rat that resolves by 1 month of age. This transitory state parallels clinical descriptions of human infants undergoing opiate abstinence.
从妊娠第8天至分娩期间，通过渗透微型泵给予两剂美沙酮，这种给药技术先前已证明会使母鼠产生身体依赖性。一对配对喂养的对照组通过微型泵接受无菌水，并且只允许其在相同妊娠天数内进食和饮水高剂量组所消耗的量。一个未处理的对照组在怀孕期间不进行干预。所有接受治疗的和对照的幼崽在出生时都寄养给未处理的母鼠。美沙酮对母体和后代毒性的影响重复了我们之前的研究结果。在29 - 31日龄时，对每只接受治疗的和对照的动物进行声学惊吓幅度变化或静息 - 活动周期测试。美沙酮处理的后代在这两项测量中与对照组没有差异。这些发现支持了我们早期研究得出的假设，即产前接触美沙酮会产生延长但短暂的阿片类药物戒断反应。这表现为惊吓幅度增加和静息 - 活动周期紊乱，在大约3周龄时达到峰值。我们证明这些影响在4周龄时不再明显。总之，这些发现定义了幼鼠的一种过度兴奋状态，这种状态在1月龄时消失。这种短暂状态与经历阿片类药物戒断的人类婴儿的临床描述相似。
