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围产期丁丙诺啡和美沙酮暴露对纹状体胆碱能个体发生的影响。

Effects of perinatal buprenorphine and methadone exposures on striatal cholinergic ontogeny.

作者信息

Robinson Susan E

机构信息

Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA 23298-0613, USA.

出版信息

Neurotoxicol Teratol. 2002 Mar-Apr;24(2):137-42. doi: 10.1016/s0892-0362(01)00185-4.

Abstract

The effects of exposure to various doses of buprenorphine, methadone or water during the perinatal period were studied on striatal cholinergic development in the rat. Rats were exposed to buprenorphine (0.3 or 3.0 mg/kg/day), methadone (9 mg/kg/day) and/or water prenatally, postnatally or both pre- and postnatally via maternally implanted osmotic minipumps. The effects of buprenorphine varied with the dose used. There were some similarities between the effects of perinatal buprenorphine and perinatal methadone, such as a reduction in striatal acetylcholine (ACh) content in 4-day-old pups exposed prenatally to methadone or buprenorphine (0.3 mg/kg/day). However, differences were also observed between the effects of the two drugs. Unlike methadone, the 0.3-mg/kg/day dose of buprenorphine produced a sex-related increase in striatal ACh in male postnatal day (PND) 21 pups. The 3-mg/kg/day dose of buprenorphine produced a completely different range of results, such as decreased striatal ACh content in 4-day-old pups exposed to the drug postnatally and in 21-day-old pups exposed both pre- and postnatally. Differences in the effects of the two drugs may be related to the different affinities and efficacies of the drugs at different opioid receptor subtypes.

摘要

研究了围产期接触不同剂量丁丙诺啡、美沙酮或水对大鼠纹状体胆碱能发育的影响。大鼠在产前、产后或产前产后通过母体植入的渗透微型泵接触丁丙诺啡(0.3或3.0毫克/千克/天)、美沙酮(9毫克/千克/天)和/或水。丁丙诺啡的作用随使用剂量而变化。围产期丁丙诺啡和美沙酮的作用有一些相似之处,例如产前接触美沙酮或丁丙诺啡(0.3毫克/千克/天)的4日龄幼崽纹状体乙酰胆碱(ACh)含量降低。然而,两种药物的作用之间也观察到差异。与美沙酮不同,0.3毫克/千克/天剂量的丁丙诺啡使雄性出生后第21天(PND)幼崽的纹状体ACh出现与性别相关的增加。3毫克/千克/天剂量的丁丙诺啡产生了完全不同的一系列结果,例如产后接触该药物的4日龄幼崽以及产前产后均接触该药物的21日龄幼崽纹状体ACh含量降低。两种药物作用的差异可能与药物在不同阿片受体亚型上的不同亲和力和效力有关。

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