Chronic methylphenidate exposure during adolescence reduces striatal synaptic responses to ethanol.
Chronic methylphenidate exposure during adolescence reduces striatal synaptic responses to ethanol.
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DOI：
10.1111/ejn.12426
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Mateo Y
中科院分区：
文献类型：
--
作者：
Crowley NA;Cody PA;Davis MI;Lovinger DM;Mateo Y
多巴胺（DA）在促进适应性行为的整合功能中起着重要作用。为了支持这一基本功能，DA调节了包括纹状体在内的不同大脑区域的突触可塑性。许多用于增强认知的药物都是精神兴奋剂，如哌醋甲酯（MPH），它可以提高DA水平。青春期是神经发育增强的时期，在此期间DA系统处于一种不稳定的状态。最近的流行病学研究报告了青少年和年轻人共同滥用MPH和乙醇的情况。尽管重复的MPH治疗会产生持久的变化，影响随后对其他精神兴奋剂的行为反应，但很少有研究调查MPH与乙醇之间的相互作用。在这里，我们研究了在青春期长期暴露于MPH是否会使小鼠对乙醇的反应发生改变，以及这是否伴随着DA释放和纹状体可塑性的改变。C57BL/6J小鼠在出生后30 ~ 60天通过饮水给予3 ~ 6 mg/kg/天的MPH。伏安实验表明，小鼠在青春期达到了足够的脑MPH浓度，从而增加了成年期DA的清除率。治疗还增加了长期抑郁，并减少了乙醇对纹状体突触反应的影响。虽然0.4或2g /kg乙醇的剂量依赖性地降低了对照组小鼠的运动能力，但只有较高剂量的乙醇降低了mph处理小鼠的运动能力。这些结果表明，在发育期间给药MPH促进了DA靶向的前脑区域突触可塑性的长期影响。这些可塑性的变化，反过来，可能是成年后由这些大脑区域控制的行为改变的基础。
Dopamine (DA) plays an important role in integrative functions contributing to adaptive behaviors. In support of this essential function, DA modulates synaptic plasticity in different brain areas, including the striatum. Many drugs used for cognitive enhancement are psychostimulants, such as methylphenidate (MPH), which enhance DA levels. MPH treatment is of interest during adolescence, a period of enhanced neurodevelopment during which the DA system is in a state of flux. Recent epidemiological studies report the co-abuse of MPH and ethanol in adolescents and young adults. Although repeated MPH treatment produces enduring changes that affect subsequent behavioral responses to other psychostimulants, few studies have investigated the interactions between MPH and ethanol. Here we addressed whether chronic therapeutic exposure to MPH during adolescence predisposed mice to an altered response to ethanol and whether this was accompanied by altered DA release and striatal plasticity. C57BL/6J mice were administered MPH (3–6 mg/kg/day) via the drinking water between post-natal days 30 and 60. Voltammetry experiments showed that sufficient brain MPH concentrations were achieved during adolescence in mice to increase the DA clearance in adulthood. The treatment also increased long-term depression and reduced the effects of ethanol on striatal synaptic responses. Although the injection of 0.4 or 2 g/kg ethanol dose-dependently decreased locomotion in control mice, only the higher dose decreased locomotion in MPH-treated mice. These results suggested that the administration of MPH during development promoted long-term effects on synaptic plasticity in forebrain regions targeted by DA. These changes in plasticity might, in turn, underlie alterations in behaviors controlled by these brain regions into adulthood.
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影响因子：
2.9
作者：
Gilabert-Juan, Javier;Dolores Molto, Maria;Nacher, Juan
通讯作者：
Nacher, Juan
影响因子：
--
作者：
Heal, David J;Smith, Sharon L;Findling, Robert L
通讯作者：
Findling, Robert L
影响因子：
4.1
作者：
Kaloyanides, Kristy B.;McCabe, Sean E.;Teter, Christian J.
通讯作者：
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影响因子：
8
作者：
Biederman, J;Wilens, T;Faraone, SV
通讯作者：
Faraone, SV
影响因子：
7.6
作者：
Brandon, CL;Marinelli, M;White, FJ
通讯作者：
White, FJ