Westerink B H, Teisman A, de Vries J B
Department of Medicinal Chemistry, University of Groningen, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Mar;349(3):230-5. doi: 10.1007/BF00169288.
The aim of the present study was to investigate the interactions between the in vivo release of dopamine and certain drugs, during conditions of increased dopaminergic activity. Dopaminergic neurons in the nucleus accumbens were activated by feeding hungry rats. 48-96 h after implantation of a microdialysis probe 30 min food ingestion by hungry rats induced an immediate eating response that was accompanied with a reproducible and long-lasting increase in extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC). The effect of various drugs (infused into the nucleus accumbens via the microdialysis probe), on the extracellular levels of dopamine and DOPAC were recorded, and the effect of eating was determined. Infusion of 5 mumol/l nomifensine and 3.4 mmol/l calcium increased dopamine release respectively 5.4 and 2-fold but did not modify the eating related increase in dopamine and DOPAC release. Infusion (1 mumol/l) as well as intraperitoneal administration (20 mg/kg) of sulpiride induced an increase in basal dopamine release to 220 and 195% of controls, respectively. Both routes of sulpiride pretreatment enhanced the eating related increase in extracellular dopamine and DOPAC. The results of the sulpiride experiments indicate that a behaviorally induced stimulation of dopamine release is modified by autoinhibition.
本研究的目的是调查在多巴胺能活性增加的情况下，多巴胺的体内释放与某些药物之间的相互作用。通过给饥饿的大鼠喂食来激活伏隔核中的多巴胺能神经元。在植入微透析探针48 - 96小时后，饥饿大鼠摄入30分钟食物会引发即时进食反应，同时细胞外多巴胺和3,4 - 二羟基苯乙酸（DOPAC）会出现可重复且持久的增加。记录了各种药物（通过微透析探针注入伏隔核）对多巴胺和DOPAC细胞外水平的影响，并确定了进食的影响。注入5 μmol/l的诺米芬辛和3.4 mmol/l的钙分别使多巴胺释放增加了5.4倍和2倍，但并未改变与进食相关的多巴胺和DOPAC释放增加。注入（1 μmol/l）以及腹腔注射（20 mg/kg）舒必利分别使基础多巴胺释放增加至对照的220%和195%。舒必利预处理的这两种途径均增强了与进食相关的细胞外多巴胺和DOPAC的增加。舒必利实验的结果表明，行为诱导的多巴胺释放刺激会受到自身抑制的调节。
