Division of Neurology, Dept. of Pediatrics, Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229-3039, United States.
Neurotoxicol Teratol. 2010 May-Jun;32(3):356-61. doi: 10.1016/j.ntt.2010.02.001. Epub 2010 Feb 11.
Rat neonatal methamphetamine exposure results in corticosterone release and learning and memory impairments in later life; effects also observed after neonatal stress. Previous attempts to test the role of corticosterone release after methamphetamine using corticosterone inhibitors were unsuccessful and adrenalectomy caused reductions in hippocampal serotonin greater than those caused by methamphetamine alone. Here we tested whether adrenal autotransplantation could be used to attenuate methamphetamine-induced corticosterone release without also altering the effects of the drug on serotonin. Adrenal autotransplantation surgery occurred on postnatal day 9 followed by methamphetamine or saline treatment from postnatal day 11-20 (10mg/kg/dosex4/day). Plasma corticosterone and hippocampal serotonin and 5-hydroxyindoleacetic acid were determined 30min following the first treatment on each day between postnatal days 11-20. Adrenal autotransplantation attenuated neonatal methamphetamine-induced corticosterone release by approximately 70% initially, approximately 55% midway through treatment, and approximately 25% by the end of treatment. Methamphetamine reduced serotonin and 5-hydroxyindoleacetic acid in the hippocampus in the ADXA rats to the same degree as in SHAM rats. The data show that neonatal adrenal autotransplantation is an effective method for partially reducing treatment-induced corticosterone release while providing sufficient corticosterone to sustain normal growth and development. The method should be applicable to other models of developmental stress/corticosterone release.
新生大鼠接触甲基苯丙胺会导致皮质酮释放，并在以后的生活中出现学习和记忆障碍；在新生期应激后也观察到这种影响。之前使用皮质酮抑制剂测试甲基苯丙胺后皮质酮释放的作用的尝试都没有成功，而且肾上腺切除术导致海马 5-羟色胺的减少大于甲基苯丙胺单独引起的减少。在这里，我们测试了肾上腺自体移植是否可以在不改变药物对 5-羟色胺的作用的情况下减轻甲基苯丙胺引起的皮质酮释放。肾上腺自体移植手术于生后第 9 天进行，然后于生后第 11-20 天（10mg/kg/dosex4/day）进行甲基苯丙胺或盐水治疗。在生后第 11-20 天的每一天的第一次治疗后 30 分钟，测定血浆皮质酮和海马 5-羟色胺和 5-羟吲哚乙酸。最初，肾上腺自体移植减轻了新生大鼠甲基苯丙胺诱导的皮质酮释放约 70%，治疗中期约 55%，治疗结束时约 25%。甲基苯丙胺将 ADXA 大鼠海马中的 5-羟色胺和 5-羟吲哚乙酸降低到与 SHAM 大鼠相同的程度。数据表明，新生期肾上腺自体移植是一种有效方法，可部分减少治疗引起的皮质酮释放，同时提供足够的皮质酮以维持正常生长和发育。该方法应适用于其他发育应激/皮质酮释放模型。
