Faculty of Science, Department of Biology, University of Urmia, Urmia, Iran.
Dev Psychobiol. 2013 Dec;55(8):881-7. doi: 10.1002/dev.21080. Epub 2012 Sep 13.
Opioids show both pro- and anti-epileptogenic effects in different experimental models of epilepsy. In the present study, the pentylentetrazole (PTZ)-induced seizure model was used to test the hypothesis that neonatal morphine administration affects seizure susceptibility in prepubertal rats. Female rats were subcutaneously injected with either morphine or saline on postnatal days 8-14 (P8-P14). To verify the long-term effect of morphine (or saline), the animals were treated second time with morphine (21 mg/kg; or saline) on either P25 or P32. Morphine administration decreased latency of myoclonic jerks and time to onset and increased tonic-clonic seizure rate at P25, but these findings were inversed at P32. Results showed a significant age difference in seizure behaviors between P25 and P32 animals. Blood corticosterone (COS) levels were significantly higher in P32 rats than in P25 rats. These findings show that neonatal morphine exposure plays an important role in increasing seizure vulnerability in P25 prepubertal rats but not in P32 rats. We conclude that early exposure to chronic morphine in infant rats might change their susceptibility to PTZ-induced seizure in an age-dependent manner.
阿片类药物在不同的癫痫实验模型中表现出促癫痫和抗癫痫的双重作用。本研究采用戊四氮（PTZ）诱导的癫痫发作模型，检验了这样一个假设，即新生期吗啡给药会影响未成年大鼠的癫痫易感性。雌性大鼠在出生后第 8-14 天（P8-P14）皮下注射吗啡或生理盐水。为了验证吗啡（或生理盐水）的长期作用，动物在 P25 或 P32 时再次接受吗啡（21mg/kg；或生理盐水）治疗。吗啡给药可降低 P25 时肌阵挛性抽搐的潜伏期、发作起始时间和强直阵挛性癫痫发作率，但在 P32 时则相反。结果显示，P25 和 P32 动物的癫痫行为存在明显的年龄差异。P32 大鼠的血皮质酮（COS）水平明显高于 P25 大鼠。这些发现表明，新生期吗啡暴露在 P25 未成年大鼠中增加了癫痫易感性，但在 P32 大鼠中没有。我们得出结论，婴儿期大鼠早期暴露于慢性吗啡可能会以年龄依赖性的方式改变其对 PTZ 诱导的癫痫发作的易感性。
