Williams Jason M, Steketee Jeffery D
Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA.
Eur J Neurosci. 2004 Sep;20(6):1639-46. doi: 10.1111/j.1460-9568.2004.03618.x.
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and were pretreated daily with saline (1 mL/kg/day x 4 days, i.p.) or cocaine (15 mg/kg/day x 4 days, i.p.) and withdrawn for 1, 7 or 30 days.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 Animals that were withdrawn from repeated daily cocaine for 1 day and 7 days displayed an augmentation in cocaine-induced mPFC glutamate levels compared to saline and acute control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.
中脑皮质边缘脑通路内的兴奋性氨基酸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。当前的研究评估了在从重复暴露于可卡因后的不同戒断期，可卡因对内侧前额叶皮质（mPFC）细胞外谷氨酸水平的影响的时间进程。雄性Sprague-Dawley大鼠接受立体定位手术，每天腹腔注射生理盐水（1 mL/kg/天×4天）或可卡因（15 mg/kg/天×4天）进行预处理，然后戒断1、7或30天。戒断后，大鼠用相同剂量的生理盐水或可卡因进行激发，并对mPFC进行体内微透析，同时分析运动活动。与生理盐水和急性对照组相比，从每日重复给予可卡因中戒断1天和7天的动物，可卡因诱导的mPFC谷氨酸水平升高，而生理盐水和急性对照组同样不受可卡因激发的影响。在7天时间点，接受重复可卡因处理的一部分动物未表现出行为敏化，这些动物对可卡因激发也未表现出mPFC谷氨酸的增强。与这些早期效应相反，30天的戒断导致无论预处理或行为反应如何，可卡因诱导的mPFC谷氨酸水平均无显著变化。这些数据表明，重复给予可卡因在戒断的第一周内会短暂增加可卡因诱导的mPFC谷氨酸水平，这可能在对可卡因的行为敏化发展中起重要作用。
