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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:青春期期间的慢性甲基酚暴露会降低对乙醇的纹状体突触反应

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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)在有助于自适应行为的综合作用中起着重要作用。为了支持这种基本功能,DA调节不同脑区的突触可塑性,包括纹状体。用于认知增强的许多药物是精神疗法,例如甲基酚(MPH),其增强DA水平。在青春期期间,MPH治疗是有益的,在其中DA系统处于通量状态的增强神经发光期。最近的流行病学研究报告了青少年和年轻成年人的共同滥用MPH和乙醇。虽然重复的MPH处理产生了影响随后对其他精神疗法的行为反应影响的持久变化,但很少研究MPH和乙醇之间的相互作用。在这里,我们在青春期预处理的小鼠期间对慢性治疗性暴露于MPH,以改变对乙醇的反应,并伴随着改变的DA释放和纹状体。通过产后日30和60之间的饮用水施用C57BL / 6J小鼠。伏安法实验表明,在小鼠中的青春期期间实现了足够的脑MPH浓度,以增加DA间隙成年。该治疗还增加了长期抑郁症,并降低了乙醇对纬度突触反应的影响。尽管在对照小鼠中注射0.4或2g / kg乙醇剂量依赖性减少的运动,但仅较高剂量降低了Mph处理的小鼠的运动。这些结果表明,发育期间的MPH促进了DA靶向前脑区突触区域的长期影响。反过来,这些可塑性变化可能是这些脑区控制到成年期的行为的改变。

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