Beyer C E, Steketee J D
Department of Pharmacology and Therapeutics and School of Graduate Studies, Louisiana State University Health Sciences Center, Shreveport 71130-3932, USA.
Psychopharmacology (Berl). 2000 Aug;151(2-3):211-8. doi: 10.1007/s002139900345.
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.
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).
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.
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 NAC.
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 acute cocaine-induced behavioral (locomotor activity) and neurochemical (DA concentrations in the NAC) responses in the rat.
大量证据表明，内侧前额叶皮质（mPFC）是介导对可卡因的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。
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。
在mPFC和NAC上方双侧植入套管一周后（用于透析实验），雄性Sprague-Dawley大鼠在经外周给予生理盐水或可卡因（15mg/kg，腹腔注射）前约5分钟，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5.0nmol）或部分DA D1样激动剂SKF 38393（每侧0.5、1.5或5.0nmol）。对于透析实验，仅检测了喹吡罗的最高剂量。
喹吡罗预处理使可卡因诱导的运动活动呈剂量依赖性降低，最高剂量导致对可卡因的急性运动兴奋反应完全消除。相比之下，在所测试的剂量下，mPFC内给予SKF 38393未显示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5nmol）显著阻断了可卡因诱导的NAC中DA溢出。
本研究结果进一步支持mPFC是可卡因部分产生其运动兴奋作用的神经基础。此外，这些数据表明，调节皮质DA D2受体可阻断大鼠急性可卡因诱导的行为（运动活动）和神经化学（NAC中DA浓度）反应。
