Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, Vrije Universiteit University Medical Center, 1081 BT Amsterdam, The Netherlands.
J Neurosci. 2011 Jan 5;31(1):262-72. doi: 10.1523/JNEUROSCI.4794-10.2011.
Acute challenges with psychostimulants such as amphetamine affect impulsive behavior in both animals and humans. With regard to amphetamine, it is important to unravel how this drug affects impulsivity since it is not only a widely abused recreational drug but also regularly prescribed to ameliorate maladaptive impulsivity. Therefore, we studied the effects of amphetamine in two rat models of impulsivity, the five-choice serial reaction time task and the delayed-reward task, providing measures of inhibitory control and impulsive choice, respectively. We focused on the role of opioid receptor activation in amphetamine-induced impulsivity as there is ample evidence indicating an important role for endogenous opioids in several behavioral and neurochemical effects of amphetamine. Results showed that amphetamine-induced inhibitory control deficits were dose-dependently attenuated by the preferential μ-opioid receptor antagonist naloxone, but not by the selective δ-opioid receptor antagonist naltrindole or κ-opioid receptor antagonist nor-BNI (nor-binaltorphimine dihydrochloride). In contrast, naloxone did not affect amphetamine-induced improvements in impulsive decision making. Naloxone also completely prevented inhibitory control deficits induced by GBR 12909 [1-(2-[bis(4-fluorophenyl)methoxy] ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride], a selective dopamine transporter inhibitor. Intracranial infusions of naloxone, the selective μ-opioid receptor antagonist CTAP (H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)), morphine, and the selective μ-opioid receptor agonist DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin acetate salt) revealed that μ-opioid receptor activation in the shell rather than the core subregion of the nucleus accumbens (NAc) modulates inhibitory control and subserves the effect of amphetamine thereon. Together, these results indicate an important role for NAc shell μ-opioid receptors in the regulation of inhibitory control, probably via an interaction between these receptors and the mesolimbic dopamine system.
急性挑战，如苯丙胺等精神兴奋剂会影响动物和人类的冲动行为。就苯丙胺而言，重要的是要解开这种药物如何影响冲动性，因为它不仅是一种广泛滥用的娱乐药物，而且还经常被开处方来改善适应不良的冲动性。因此，我们在两种冲动性大鼠模型中研究了苯丙胺的作用，即五选择序列反应时间任务和延迟奖励任务，分别提供了抑制控制和冲动选择的测量。我们专注于阿片受体激活在苯丙胺引起的冲动性中的作用，因为有大量证据表明内源性阿片在苯丙胺的几种行为和神经化学作用中起着重要作用。结果表明，阿片受体选择性拮抗剂纳洛酮剂量依赖性地减弱了苯丙胺诱导的抑制控制缺陷，但选择性 δ-阿片受体拮抗剂纳曲吲哚或 κ-阿片受体拮抗剂 nor-BNI（nor-binaltorphimine dihydrochloride）则没有。相反，纳洛酮对苯丙胺诱导的冲动决策改善没有影响。纳洛酮也完全阻止了 GBR 12909 [1-(2-[bis(4-fluorophenyl)methoxy] ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride]诱导的抑制控制缺陷，GBR 12909 是一种选择性多巴胺转运体抑制剂。纳洛酮、选择性 μ-阿片受体拮抗剂 CTAP（H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)）、吗啡和选择性 μ-阿片受体激动剂 DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin acetate salt)的颅内输注表明，伏隔核（NAc）壳而非核区 μ-阿片受体的激活调节抑制控制，并对其起作用。综上所述，这些结果表明 NAc 壳 μ-阿片受体在调节抑制控制中起着重要作用，可能是通过这些受体与中脑边缘多巴胺系统之间的相互作用。
