Koffarnus Mikhail N, Newman Amy H, Grundt Peter, Rice Kenner C, Woods James H
Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
Behav Pharmacol. 2011 Aug;22(4):300-11. doi: 10.1097/FBP.0b013e3283473bcb.
Impulsivity is widely regarded as a multidimensional trait that encompasses two or more distinct patterns of behavior, and dopaminergic systems are implicated in the expression of impulsive behavior in both humans and animal subjects. Impulsive choice, or the tendency to choose rewards associated with relatively little or no delay, has been extensively studied in humans and animal subjects using delay-discounting tasks. Here, delay-discounting procedures were used to assess the effects of receptor-selective dopaminergic agonists, antagonists, and dopamine transporter ligands on choices of immediate versus delayed sucrose pellets. The effects of d-amphetamine, GBR 12909, apomorphine, SKF 81297, sumanirole, pramipexole, ABT-724, SCH 23390, L-741,626, PG01037, and L-745,870 were assessed in 24 Sprague-Dawley rats. The only drugs to affect impulsive choice selectively without altering undelayed choice were the D1-like antagonist, SCH 23390 (0.01 mg/kg), and the D4 partial agonist, ABT-724 (3.2 mg/kg), which both increased impulsive choice. The shared effects of these compounds may be explained by their localization within the prefrontal cortex on different groups of neurons. None of the selective agonists and antagonists tested reduced impulsive choice, so further research is needed to determine if direct dopaminergic agonists or antagonists may be therapeutically useful in the treatment of impulse-control disorders.
冲动性被广泛认为是一种多维度特质，它包含两种或更多不同的行为模式，并且多巴胺能系统与人类和动物受试者的冲动行为表达有关。冲动选择，即选择与相对较少延迟或无延迟相关的奖励的倾向，已在人类和动物受试者中通过延迟折扣任务进行了广泛研究。在此，使用延迟折扣程序来评估受体选择性多巴胺能激动剂、拮抗剂和多巴胺转运体配体对即时与延迟蔗糖颗粒选择的影响。在24只Sprague-Dawley大鼠中评估了右旋苯丙胺、GBR 12909、阿扑吗啡、SKF 81297、舒马曲坦、普拉克索、ABT-724、SCH 23390、L-741,626、PG01037和L-745,870的作用。唯一能选择性影响冲动选择而不改变无延迟选择的药物是D1样拮抗剂SCH 23390（0.01 mg/kg）和D4部分激动剂ABT-724（3.2 mg/kg），它们都增加了冲动选择。这些化合物的共同作用可能是由于它们在前额叶皮质内不同神经元群体上的定位。所测试的选择性激动剂和拮抗剂均未减少冲动选择，因此需要进一步研究以确定直接多巴胺能激动剂或拮抗剂在治疗冲动控制障碍方面是否具有治疗作用。
