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首页> 外文期刊>The European Journal of Neuroscience >Cocaine increases medial prefrontal cortical glutamate overflow in cocaine-sensitized rats: a time course study.
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Cocaine increases medial prefrontal cortical glutamate overflow in cocaine-sensitized rats: a time course study.

机译：可卡因增加可卡因致敏大鼠的内侧前额叶皮质谷氨酸溢流：一项时程研究。

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Abstract Excitatory amino acid transmission within mesocorticolimbic brain pathways is thought to play an important role in behavioural sensitization to psychomotor stimulants. The current studies evaluated a time course of the effects of cocaine on extracellular glutamate levels within the medial prefrontal cortex (mPFC) following increasing periods of withdrawal from repeated cocaine exposure. Male Sprague-Dawley rats underwent stereotaxic surgeries and were pretreated daily with saline (1 mL/kg/day x 4 days, i.p.) or cocaine (15 mg/kg/day x 4 days, i.p.) and withdrawn for 1, 7 or 30 days. After withdrawal rats were challenged with the same dose of saline or cocaine and in vivo microdialysis of the mPFC was conducted with concurrent analysis of locomotor activity. Animals that were withdrawn from repeated daily cocaine for 1 day and 7 days displayed an augmentation in cocaine-induced mPFC glutamate levels compared to saline and acute control subjects, which were similarly unaffected by cocaine challenge. At the 7 day time point, a subset of animals that received repeated cocaine did not express behavioural sensitization, nor did these animals exhibit the enhancement in mPFC glutamate in response to cocaine challenge. In contrast to these early effects, 30 days of withdrawal resulted in no significant changes in cocaine-induced mPFC glutamate levels regardless of the pretreatment or behavioural response. These data suggest that repeated cocaine administration transiently increases cocaine-induced glutamate levels in the mPFC during the first week of withdrawal, which may play an important role in the development of behavioural sensitization to cocaine.
机译：摘要兴奋性氨基酸在中皮层皮质脑途径中的传递被认为在对精神运动兴奋剂的行为敏化中起重要作用。目前的研究评估了可卡因对反复暴露于可卡因的撤药时间增加后，对内侧前额叶皮层（mPFC）中细胞外谷氨酸水平的影响随时间变化。雄性Sprague-Dawley大鼠经过立体定向手术，每天接受生理盐水（1 mL / kg /天x 4天，ip）或可卡因（15 mg / kg /天x 4天，ip）预处理，并停药1、7或30天。戒断后，用相同剂量的生理盐水或可卡因攻击大鼠，并在体内对mPFC进行微透析，并同时分析运动活性。与盐水和急性对照受试者相比，每天反复重复可卡因撤离1天和7天的动物表现出可卡因诱导的mPFC谷氨酸水平增加，这同样不受可卡因攻击的影响。在第7天的时间点，接受重复可卡因治疗的一部分动物既未表现出行为敏化作用，也未响应可卡因攻击而表现出mPFC谷氨酸的增强。与这些早期影响相反，撤药30天不会导致可卡因诱导的mPFC谷氨酸水平的明显变化，而与预处理或行为反应无关。这些数据表明，重复服用可卡因可在停药后的第一周内短暂增加可卡因诱导的mPFC中的谷氨酸水平，这可能在对可卡因的行为敏感性发展中起重要作用。

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