Schrott Lisa M, Sparber Sheldon B
Department of Pharmacology and Therapeutics, Louisiana State University Health Sciences Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71130-3932, USA.
Brain Behav Immun. 2004 Nov;18(6):515-25. doi: 10.1016/j.bbi.2003.12.006.
We have established procedures to reliably induce opiate dependence in the chick embryo via in ovo injection, early in embryonic development, of the long-acting and potent opiate N-desmethyl-l-alpha-noracetylmethadol (NLAAM). Prior studies found that there is continual exposure to NLAAM throughout embryogenesis and shortly after hatching there are signs of spontaneous withdrawal. In the present study, we used three doses of NLAAM (2.5, 5, and 10 mg/kg egg weight) to determine if prenatal opiate exposure followed by postnatal withdrawal interfered with appropriate neural-endocrine-immune interactions in the young chick. To ensure that effects were not a consequence of inappropriately large doses, we first examined acute and chronic toxicity and additional characteristics of postnatal opiate withdrawal. We then measured the corticosterone and fever responses to LPS stimulation during the withdrawal period. After the conclusion of opiate withdrawal, we assessed the hypersensitivity response to phytohemagglutinin (PHA). The fever response to LPS and the hypersensitivity response to PHA were suppressed by prenatal opiate exposure and postnatal withdrawal. The corticosterone response to LPS was not affected, but there were exaggerated corticosterone responses to saline injection in chicks exposed in ovo to NLAAM. It was unlikely that the effects of prenatal NLAAM were the result of toxicity, as little chronic toxicity was seen with the lower two doses of NLAAM, doses that yielded significant suppressions of neural-endocrine-immune responses. However, effects found in the chicks treated with 10 mg NLAAM/kg may have been partly related to the greater toxicity and/or protracted postnatal withdrawal in this group.
我们已经建立了相关程序，可通过在胚胎发育早期对鸡胚进行卵内注射长效且强效的阿片类药物N-去甲基-L-α-去乙酰美沙酮（NLAAM）来可靠地诱导阿片类药物依赖。先前的研究发现，在整个胚胎发育过程中鸡胚持续接触NLAAM，并且在孵化后不久就有自发戒断的迹象。在本研究中，我们使用了三种剂量的NLAAM（2.5、5和10mg/kg蛋重）来确定产前阿片类药物暴露后接着产后戒断是否会干扰幼鸡中适当的神经-内分泌-免疫相互作用。为确保这些影响不是由剂量过大不当所致，我们首先检查了急性和慢性毒性以及产后阿片类药物戒断的其他特征。然后，我们在戒断期测量了对脂多糖（LPS）刺激的皮质酮和发热反应。在阿片类药物戒断结束后，我们评估了对植物血凝素（PHA）的超敏反应。产前阿片类药物暴露和产后戒断抑制了对LPS的发热反应以及对PHA的超敏反应。对LPS的皮质酮反应未受影响，但在卵内暴露于NLAAM的雏鸡中，对盐水注射的皮质酮反应有所增强。产前NLAAM的影响不太可能是毒性作用的结果，因为较低的两剂量NLAAM几乎没有显示出慢性毒性，而这两个剂量却能显著抑制神经-内分泌-免疫反应。然而，用10mg NLAAM/kg处理的雏鸡中发现的影响可能部分与该组中更大的毒性和/或产后戒断时间延长有关。
