Sex and dose-related differences in methylphenidate adolescent locomotor sensitization and effects on brain-derived neurotrophic factor
Sex and dose-related differences in methylphenidate adolescent locomotor sensitization and effects on brain-derived neurotrophic factor
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DOI：
10.1177/0269881112454227
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发表时间：
2012-11-01
影响因子：
4.1
通讯作者：
Pond, Brooks B.
中科院分区：
文献类型：
--
作者：
Brown, Russell W.;Hughes, Benjamin A.;Pond, Brooks B.
本研究分析了哌醋甲酯（MPH）重复给药及其对雄性和雌性青春期大鼠背侧纹状体和延髓核中脑源性神经营养因子（BDNF）的影响。在实验1中，从出生后第33天（P）至P49天，每隔一天腹膜内（ip）给予大鼠生理盐水、1、3或5 mg/kg剂量的MPH。每次给药后分析自发活动10 min。结果表明，1 mg/kg剂量的MPH产生运动抑制，然而，5 mg/kg剂量的MPH产生运动敏化和强大的行为激活的女性相比，男性。在实验2中，使用相同的方案向动物ip施用盐水或5 mg/kg剂量的MPH，但采用30 min行为测试。在P50测定背侧纹状体和背侧核组织的BDNF。与男性相比，女性表现出对MPH的敏感性和运动激活增加。有趣的是，与对照组相比，给予MPH的女性表现出纹状体BDNF显著减少42%，而给予MPH的男性表现出纹状体BDNF显著增加50.4%。对脑源性BDNF无明显影响。这份报告显示了强大的性别差异的行为反应，但性别依赖性的变化，在纹状体BDNF在响应MPH在青春期。
This study analyzed repeated methylphenidate (MPH) administration and its effects on brain-derived neurotrophic factor (BDNF) in the dorsal striatum and nucleus accumbens of male and female adolescent rats. In Experiment 1, rats were administered intraperitoneal (ip) saline, 1, 3, or 5 mg/kg dose of MPH every second day from postnatal day (P) 33-P49. Locomotor activity was analyzed for 10 min after each administration. Results revealed that the 1 mg/kg dose of MPH produced locomotor suppression, however, the 5 mg/kg dose of MPH produced locomotor sensitization and robust behavioral activation in females as compared to males. In Experiment 2, animals were administered ip saline or the 5 mg/kg dose of MPH using an identical regimen but a 30 min behavioral test was employed. Dorsal striatum and nucleus accumbens tissue was assayed for BDNF at P50. Females demonstrated sensitization to MPH and increased locomotor activation compared to males. Interestingly, females given MPH demonstrated a significant 42% decrease of striatal BDNF whereas males administered MPH demonstrated a significant 50.4% increase of striatal BDNF compared to controls. There were no effects on accumbal BDNF. This report demonstrates robust sex differences in the behavioral response, but sex-dependent changes in striatal BDNF in response to MPH in adolescence.