Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum.
Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum.
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DOI：
10.1111/j.1460-9568.2010.07294.x
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Steiner H
中科院分区：
文献类型：
--
作者：
Van Waes V;Beverley J;Marinelli M;Steiner H
精神兴奋剂哌醋甲酯（利他林）与选择性5 -羟色胺再摄取抑制剂（SSRIs）联合使用，用于治疗诸如伴有焦虑/抑郁共病的注意力缺陷多动障碍和重度抑郁症等疾病。同时暴露也发生在使用精神兴奋剂“认知增强剂”的SSRIs患者身上。哌醋甲酯是一种多巴胺/去甲肾上腺素再摄取抑制剂，能改变前脑的基因表达；这些影响部分模仿了可卡因（多巴胺/去甲肾上腺素/血清素再摄取抑制剂）的基因调节。我们研究了SSRIs（氟西汀或西酞普兰；5 mg/kg）的加入是否改变了青春期大鼠纹状体和皮层中哌醋酯（2-5 mg/kg）的基因调控。我们的研究结果表明，SSRIs增强了甲基苯甲酸诱导纹状体中转录因子zif 268和c-fos的表达，使这些分子变化更像可卡因。纹状体的大部分都有这种增强，其中感觉运动部分的增强最为强烈。哌甲酯+ SSRI组合也增强了行为刻板印象，与感觉运动纹状体回路功能障碍一致。到目前为止，这种基因调控与精神兴奋剂成瘾有关，我们的研究结果表明，SSRIs可能会增加哌醋甲酯的成瘾倾向。
The psychostimulant methylphenidate (Ritalin) is used in conjunction with selective serotonin reuptake inhibitors (SSRIs) in the treatment of medical conditions such as attention-deficit hyperactivity disorder with anxiety/depression comorbidity and major depression. Co-exposure also occurs in patients on SSRIs that use psychostimulant “cognitive enhancers”. Methylphenidate is a dopamine/norepinephrine reuptake inhibitor that produces altered gene expression in the forebrain; these effects partly mimic gene regulation by cocaine (dopamine/norepinephrine/serotonin reuptake inhibitor). We investigated whether the addition of SSRIs (fluoxetine or citalopram; 5 mg/kg) modified gene regulation by methylphenidate (2–5 mg/kg) in the striatum and cortex of adolescent rats. Our results show that SSRIs potentiate methylphenidate-induced expression of the transcription factors zif 268 and c-fos in the striatum, rendering these molecular changes more cocaine-like. Present throughout most of the striatum, this potentiation was most robust in its sensorimotor parts. The methylphenidate + SSRI combination also enhanced behavioral stereotypies, consistent with dysfunction in sensorimotor striatal circuits. In so far as such gene regulation is implicated in psychostimulant addiction, our findings suggest that SSRIs may enhance the addiction liability of methylphenidate.
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影响因子：
5
作者：
BENLOUCIF, S;GALLOWAY, MP
通讯作者：
GALLOWAY, MP
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作者：
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通讯作者：
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