King D, Zigmond M J, Finlay J M
Department of Neuroscience, University of Pittsburgh, PA 15260, USA.
Neuroscience. 1997 Mar;77(1):141-53. doi: 10.1016/s0306-4522(96)00421-6.
In the present study we examined whether depletion of dopamine in the medial prefrontal cortex alters the neurochemical activity of mesoaccumbens dopamine neurons and/or their behavioral correlate, motor behavior. Infusion of 6-hydroxydopamine (1 microgram) into the medial prefrontal cortex of rats pretreated with a norepinephrine uptake blocker produced a 70% loss of tissue dopamine, with relative sparing of the norepinephrine content (-23%) in that region. Using in vivo microdialysis, we monitored basal and evoked extracellular dopamine in the nucleus accumbens core and shell of control and lesioned rats. The concentration of basal extracellular dopamine in the nucleus accumbens core was similar in control and lesioned rats; however, basal dopamine efflux in the nucleus accumbens shell was approximately 30% higher in lesioned rats than in controls. Lesions did not alter the ability of systemic D-amphetamine (1.5 mg/kg, i.p.) to increase extracellular dopamine in the nucleus accumbens shell, in contrast, the dopamine depletion in the medial prefrontal cortex attenuated the amphetamine-induced increase in extracellular dopamine in the nucleus accumbens core, as well as the amphetamine-induced increase in locomotor activity. Lesions did not significantly alter the effects of tail pressure (30 min) on extracellular dopamine in the nucleus accumbens core. However, the depletion of dopamine in the medial prefrontal cortex potentiated the stress-induced increase in extracellular dopamine in the nucleus accumbens shell. These data demonstrate that mesocortical dopamine neurons influence (i) amphetamine-induced dopamine efflux in the nucleus accumbens core and (ii) stress-evoked dopamine efflux in the nucleus accumbens shell. It has been proposed that a disruption in the interaction between cortical and subcortical dopamine neurons is involved in the pathophysiology of schizophrenia. The present data raise the possibility that a disruption in the interaction between mesocortical dopamine neurons and dopamine neurons projecting to the nucleus accumbens shell is involved in those symptoms of schizophrenia that are influenced by stress.
在本研究中，我们检测了内侧前额叶皮质中多巴胺的耗竭是否会改变中伏隔核多巴胺神经元的神经化学活性和/或其行为关联——运动行为。将6-羟基多巴胺（1微克）注入经去甲肾上腺素摄取阻滞剂预处理的大鼠内侧前额叶皮质，导致该区域组织多巴胺损失70%，而去甲肾上腺素含量相对保留（-23%）。我们使用体内微透析技术，监测了对照大鼠和损伤大鼠伏隔核核心区和壳区的基础及诱发的细胞外多巴胺水平。对照大鼠和损伤大鼠伏隔核核心区的基础细胞外多巴胺浓度相似；然而，损伤大鼠伏隔核壳区的基础多巴胺外流比对照大鼠高约30%。损伤并未改变全身性D-苯丙胺（1.5毫克/千克，腹腔注射）增加伏隔核壳区细胞外多巴胺的能力，相反，内侧前额叶皮质中的多巴胺耗竭减弱了苯丙胺诱导的伏隔核核心区细胞外多巴胺增加以及苯丙胺诱导的运动活动增加。损伤并未显著改变尾部加压（30分钟）对伏隔核核心区细胞外多巴胺的影响。然而，内侧前额叶皮质中多巴胺的耗竭增强了应激诱导的伏隔核壳区细胞外多巴胺增加。这些数据表明，中皮质多巴胺神经元影响（i）苯丙胺诱导的伏隔核核心区多巴胺外流和（ii）应激诱发的伏隔核壳区多巴胺外流。有人提出，皮质和皮质下多巴胺神经元之间相互作用的破坏参与了精神分裂症的病理生理学过程。目前的数据增加了一种可能性，即中皮质多巴胺神经元与投射到伏隔核壳区的多巴胺神经元之间相互作用的破坏参与了精神分裂症中受应激影响的那些症状。
