Effects of MDMA ("ecstasy") during adolescence on place conditioning and hippocampal neurogenesis
Effects of MDMA ("ecstasy") during adolescence on place conditioning and hippocampal neurogenesis
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DOI：
10.1016/j.ejphar.2009.11.017
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发表时间：
2010-02-25
影响因子：
5
通讯作者：
Sanchez-Ramos, Juan
中科院分区：
文献类型：
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作者：
Catlow, Briony J.;Badanich, Kimberly A.;Sanchez-Ramos, Juan
在青春期使用摇头丸中的活性剂3，4-亚甲二氧基甲基苯丙胺（MDMA）是普遍的，但对青少年行为和大脑发育的影响尚不清楚。本研究的目的是：1）使用条件性位置偏好（CPP）范式评估MDMA对青春期大鼠的影响，以测量MDMA诱导的奖励; 2）评估MDMA给药对海马齿状回细胞增殖、存活和神经发生的影响。在青少年时期，通过训练大鼠将1.25、2.5、5.0 mg/kg MDMA或生理盐水给药与环境线索相关联，测量了青少年[出生后（PND）28-39天]的MDMA CPP。CPP结束后，注射溴脱氧尿苷（BrdU），并在最后一次注射MDMA后24小时（评价细胞增殖）或2周（评估神经发生）对大鼠实施安乐死。青少年对2.5 mg/kg MDMA表现出CPP。在青春期重复暴露于5.0 mg/kg MDMA可增加细胞增殖，但减少神经发生，这一效应可使用流式细胞术复制。这些发现表明青少年MDMA暴露对奖励相关行为和海马神经发生的剂量效应不同。(C)2009 Elsevier B. V.保留所有权利。
The use of 3,4,methylenedioxymethamphetamine (MDMA), the active agent in ecstasy, during adolescence is widespread yet the effects on adolescent behavior and brain development are unknown. The aim of the present study was 1) to evaluate effects of MDMA in adolescent rats using the conditioned place preference (CPP) paradigm to measure MDMA-induced reward and 2) assess effects of MDMA administration on cellular proliferation, survival and neurogenesis in the dentate gyrus of the hippocampus. During the adolescent period, MDMA CPP was measured in adolescents [postnatal day (PND) 28-39] by training rats to associate 1.25, 2.5, 5.0 mg/kg MDMA or saline administration with environmental cues. After CPP ended, bromodeoxyuridine (BrdU) was injected and rats were euthanized either 24 h (to evaluate cell proliferation) or 2 weeks (to assess neurogenesis) after the last MDMA injection. Adolescents expressed a CPP for 2.5 mg/kg MDMA. Repeated exposure to 5.0 mg/kg MDMA during adolescence increased cell proliferation, yet diminished neurogenesis, an effect that was replicated using flow cytometry. These findings suggest differential dose effects of adolescent MDMA exposure on reward related behaviors and hippocampal neurogenesis. (C) 2009 Elsevier B.V. All rights reserved.