Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a.
Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a.
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DOI：
10.1111/adb.12067
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发表时间：
2014-11
影响因子：
3.4
通讯作者：
Steiner H
中科院分区：
文献类型：
--
作者：
Van Waes V;Vandrevala M;Beverley J;Steiner H
越来越多的精神兴奋剂，如哌甲酯（利他林;多巴胺再摄取抑制剂）用于医疗和健康认知增强剂。已知哌醋甲酯会产生一些与成瘾相关的基因调控。最近在动物模型中的研究结果表明，选择性5-羟色胺再摄取抑制剂（SSRI），包括氟西汀可以加强急性诱导基因表达的哌甲酯，从而表明急性促进作用，多巴胺诱导的基因调控的5-羟色胺。我们研究了在青春期大鼠中反复暴露于氟西汀联合哌甲酯是否促进了反复暴露于非法精神兴奋剂（如可卡因）的基因调节效应-基因诱导物的钝化（抑制）。我们测量，通过原位杂交组织化学，5天重复治疗哌甲酯（5毫克/公斤），氟西汀（5毫克/公斤）或组合的诱导（可卡因）的纹状体中的神经可塑性相关基因（Zif 268，Homer 1a）的影响。重复哌醋甲酯单独治疗产生最小的基因钝化，而氟西汀单独没有影响。相比之下，氟西汀添加到哌甲酯强烈增强哌甲酯诱导的两个基因的钝化。这种增强作用在整个纹状体中广泛存在，但在外侧感觉运动纹状体中最为强烈，因此模仿了可卡因的作用。对于非法精神兴奋剂，基因表达的钝化被认为是成瘾分子基础的一部分。因此，我们的研究结果表明，SSRIs如氟西汀可能会增加哌醋甲酯的成瘾倾向。
There is a growing use of psychostimulants such as methylphenidate (Ritalin; dopamine reuptake inhibitor) for medical treatments and as cognitive enhancers in the healthy. Methylphenidate is known to produce some addiction-related gene regulation. Recent findings in animal models show that selective serotonin reuptake inhibitors (SSRIs) including fluoxetine can potentiate acute induction of gene expression by methylphenidate, thus indicating an acute facilitatory role for serotonin in dopamine-induced gene regulation. We investigated whether repeated exposure to fluoxetine in conjunction with methylphenidate in adolescent rats facilitated a gene regulation effect well-established for repeated exposure to illicit psychostimulants such as cocaine - blunting (repression) of gene inducibility. We measured, by in situ hybridization histochemistry, the effects of a 5-day repeated treatment with methylphenidate (5 mg/kg), fluoxetine (5 mg/kg) or a combination on the inducibility (by cocaine) of neuroplasticity-related genes (Zif268, Homer1a) in the striatum. Repeated methylphenidate treatment alone produced minimal gene blunting, while fluoxetine alone had no effect. In contrast, fluoxetine added to methylphenidate robustly potentiated methylphenidate-induced blunting for both genes. This potentiation was widespread throughout the striatum, but was most robust in the lateral, sensorimotor striatum, thus mimicking cocaine effects. For illicit psychostimulants, blunting of gene expression is considered part of the molecular basis of addiction. Our results thus suggest that SSRIs such as fluoxetine may increase the addiction liability of methylphenidate.
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影响因子：
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Chase, T.;Carrey, N.;Wilkinson, M.
通讯作者：
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通讯作者：
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