Intra-medial prefrontal cortex injection of quinpirole, but not SKF 38393, blocks the acute motor-stimulant response to cocaine in the rat
Intra-medial prefrontal cortex injection of quinpirole, but not SKF 38393, blocks the acute motor-stimulant response to cocaine in the rat
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DOI：
10.1007/s002139900345
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发表时间：
2000-08-01
影响因子：
3.4
通讯作者：
Steketee, JD
中科院分区：
文献类型：
--
作者：
Beyer, CE;Steketee, JD
理由：大量证据表明内侧前额叶皮层 (mPFC) 是调节可卡因某些行为和神经化学反应的重要区域。然而，皮质多巴胺 (DA) 受体亚型在调节这些反应中的作用尚未阐明。目的：本研究调查了 mPFC 内给予 DA 激动剂对可卡因急性运动兴奋反应的影响。此外，采用体内微透析技术来确定皮质内注射对伏隔核（NAC）中可卡因诱导的细胞外 DA 浓度的影响。方法：在 mPFC 和 NAC 上植入双侧插管（用于透析实验）一周后，雄性 Sprague-Dawley 大鼠接受 mPFC 内注射生理盐水、DA D2 样激动剂喹吡罗（每侧 0.015、0.05、0.15、0.5、1.5 或 5.0 nmol）或部分 DA D1 样激动剂SKF 38393（每侧 0.5、1.5 或 5.0 nmol）在外周注射生理盐水或可卡因（15 mg/kg，腹腔注射）前约 5 分钟。对于透析实验，仅检查最高剂量的喹吡罗。结果：喹吡罗预处理可导致可卡因诱导的运动活动出现剂量依赖性下降，最高剂量可完全消除对可卡因的急性运动刺激反应。相比之下，在测试剂量下，mPFC 内施用 SKF 38393 并未显示出改变可卡因诱导的运动活动。与行为效应一致，mPFC 内注射喹吡罗（每侧 5 nmol）显着阻断了 NAG 中可卡因诱导的 DA 溢出。结论：本研究的结果提供了额外的支持，即 mPFC 是一种神经基质，可卡因部分通过它产生运动刺激作用。此外，这些数据表明，皮质 DA D2 受体的调节可以阻断可卡因诱导的大鼠行为（运动活动）和神经化学（NAC 中的 DA 浓度）反应。
Rationale: Considerable evidence suggests that the medial prefrontal cortex (mPFC) is an important region in mediating certain behavioral and neurochemical responses to cocaine. However, a role for cortical dopamine (DA) receptor subtypes in modulating these responses has yet to be elucidated. Objectives: This study investigated the effects of intra-mPFC administration of DA agonists on the acute motor-stimulant response to cocaine. In addition, in vivo microdialysis techniques were employed to determine the effects of intracortical injection on cocaine-induced extracellular DA concentrations in the nucleus accumbens (NAC). Methods: One week following bilateral cannulae implantation over the mPFC and the NAC (for dialysis experiments), male Sprague-Dawley rats received an intra-mPFC injection of saline, the DA D2-like agonist quinpirole (0.015, 0.05, 0.15, 0.5, 1.5, or 5.0 nmol per side) or the partial DA D1-like agonist SKF 38393 (0.5, 1.5, or 5.0 nmol per side) approximately 5 min before peripheral administration of saline or cocaine (15 mg/kg, i.p.). For dialysis experiments, only the highest dose of quinpirole was examined. Results: Pretreatment with quinpirole produced a dose-dependent decrease in cocaine-induced motor activity, with the highest doses resulting in a complete abolition of the acute motor-stimulant response to cocaine. In contrast, intra-mPFC administration of SKF 38393 was not shown, at the doses tested, to alter cocaine-induced motor activity. In agreement with the behavioral effects, intra-mPFC quinpirole injection (5 nmol per side) significantly blocked cocaine-induced DA overflow in the NAG. Conclusions: The results of the present study provide additional support that the mPFC is a neural substrate through which cocaine, in part, produces its motor-stimulant effects. In addition, these data suggest that modulation of cortical DA D2 receptors can block;scute cocaine-induced behavioral (locomotor activity) and neurochemical (DA concentrations in the NAC) responses in the rat.