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首页> 外文期刊>The European Journal of Neuroscience >Chronic methylphenidate exposure during adolescence reduces striatal synaptic responses to ethanol
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Chronic methylphenidate exposure during adolescence reduces striatal synaptic responses to ethanol

机译：青春期慢性哌醋甲酯暴露可降低纹状体对乙醇的突触反应

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摘要

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.
机译：多巴胺（DA）在有助于适应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调节包括纹状体在内的不同大脑区域的突触可塑性。用于提高认知能力的许多药物是精神兴奋剂，例如哌醋甲酯（MPH），可提高DA水平。 MPH治疗在青春期是令人感兴趣的，青春期是神经发育增强的时期，在此期间DA系统处于通量状态。最近的流行病学研究报道了青少年和年轻人中MPH和乙醇的共同滥用。尽管反复进行MPH治疗会产生持久变化，从而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，我们探讨了青春期期间慢性治疗性MPH暴露是否会使小鼠对乙醇的反应发生改变，以及是否伴随着DA释放和纹状体可塑性的改变。在出生后30至60天之间，通过饮用水对C57BL / 6J小鼠进行MPH（3-6 mg / kg /天）给药。伏安法实验表明，青春期期间小鼠达到了足够的脑MPH浓度，从而增加了DA的清除率。成年。该治疗还增加了长期抑郁，并降低了乙醇对纹状体突触反应的影响。尽管在对照组小鼠中注射0.4或2 g / kg乙醇会剂量依赖性地降低运动能力，但只有更高剂量的MPH处理小鼠才能降低运动能力。这些结果表明，在发育过程中施用MPH促进了DA靶向的前脑区域对突触可塑性的长期影响。这些可塑性的变化可能反过来是由这些大脑区域控制到成年的行为改变的基础。

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