Li Yijing, Zuo Yanfang, Yu Peng, Ping Xingjie, Cui Cailian
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Xueyuan Road 38#, Haidian District, 100191 Beijing, PR China.
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Xueyuan Road 38#, Haidian District, 100191 Beijing, PR China.
Behav Brain Res. 2015;287:187-95. doi: 10.1016/j.bbr.2015.03.039. Epub 2015 Mar 28.
Psychostimulant substances have been found to either increase or inhibit impulsive choice (preference to choose small immediate reward over large delayed reward) in laboratory animals. Although central dopamine transmission has been demonstrated to be involved in impulsivity and drug addiction, little is known regarding dopaminergic neurotransmission in addictive drug-induced alteration of impulse control. In this study, we used a delay discounting model to measure impulsive choice in rats and found that acute cocaine dose-dependently decreased impulsive choice in rats. Intraperitoneal injection (i.p.) of D1 receptor antagonist SCH23390 (0.02 mg/kg) could increase the impulsive choice but had no effect on the inhibition of impulsive choice induced by acute cocaine exposure. D2 receptor antagonist eticlopride (0.06 mg/kg) had no effect on the choice behavior itself, but it reversed acute cocaine-induced impulse inhibition. Moreover, bilateral microinjection of eticlopride (1 μg/side) into the basolateral amygdala (BLA) but not the nucleus accumbens (NAc) core reversed the inhibitory effect of acute cocaine on impulsive choice. These data suggest important but dissociable roles of dopamine D1 and D2 receptors in impulse control. The preference of delayed rewards depends on D1 receptors, whereas acute cocaine inhibited impulsive choice by activating D2 receptors in the BLA.
在实验动物中，人们发现精神刺激物质既能增加也能抑制冲动选择（相较于大的延迟奖励更倾向于选择小的即时奖励）。尽管中枢多巴胺传递已被证明与冲动性和药物成瘾有关，但关于成瘾性药物引起的冲动控制改变中的多巴胺能神经传递，我们所知甚少。在本研究中，我们使用延迟折扣模型来测量大鼠的冲动选择，发现急性给予可卡因能剂量依赖性地降低大鼠的冲动选择。腹腔注射（i.p.）D1受体拮抗剂SCH23390（0.02mg/kg）可增加冲动选择，但对急性可卡因暴露诱导的冲动选择抑制没有影响。D2受体拮抗剂依替必利（0.06mg/kg）对选择行为本身没有影响，但它可逆转急性可卡因诱导的冲动抑制。此外，双侧向基底外侧杏仁核（BLA）而非伏隔核（NAc）核心微量注射依替必利（1μg/侧）可逆转急性可卡因对冲动选择的抑制作用。这些数据表明多巴胺D1和D2受体在冲动控制中起重要但可分离的作用。对延迟奖励的偏好取决于D1受体，而急性可卡因通过激活BLA中的D2受体来抑制冲动选择。
