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N-甲基-D-天冬氨酸受体2B亚基(GluN2B)选择性拮抗剂对雄性大鼠延迟和概率折扣的影响:延迟/概率呈现顺序的调节作用

Effects of GluN2B-selective antagonists on delay and probability discounting in male rats: Modulation by delay/probability presentation order.

作者信息

Yates Justin R, Prior Nicholas A, Chitwood Marissa R, Day Haley A, Heidel Jonah R, Hopkins Sarah E, Muncie Brittany T, Paradella-Bradley Tatiana A, Sestito Alexandra P, Vecchiola Ashley N, Wells Emily E

机构信息

Department of Psychological Science.

Department of Psychological and Brain Sciences.

出版信息

Exp Clin Psychopharmacol. 2018 Dec;26(6):525-540. doi: 10.1037/pha0000216. Epub 2018 Jul 23.

Abstract

The contribution of the GluN2B subunit of the NMDA receptor to impulsivity has recently been examined. Ro 63-1908, a highly selective antagonist for the GluN2B, decreases impulsive choice. Because the order in which delays are presented modulates drug effects in discounting procedures, one goal of the current study was to determine the effects of Ro 63-1908 in delay discounting procedures in which the delays to obtaining the large reinforcer either increase or decrease across the session. We also determined if Ro 63-1908 differentially alters risky choice in probability discounting procedures that use ascending/descending schedules. Male rats were trained in either delay ( = 24) or probability ( = 24) discounting in which the delay to/odds against reinforcement were presented in either ascending or descending order ( = 12 each schedule). Following training, rats received the GluN2B antagonists Ro 63-1908 (0-1.0 mg/kg) and CP-101,606 (0-3.0 mg/kg). In delay discounting, Ro 63-1908 (1.0 mg/kg), but not CP-101,606, decreased choice for the large reinforcer, but only when the delays decreased across the session. In probability discounting, Ro 63-1908 (0.3 mg/kg)/CP-101,606 (1.0 mg/kg) increased choice for the large reinforcer when the probability of obtaining this alternative decreased across the session, but Ro 63-1908 (1.0 mg/kg)/CP-101,606 (3.0 mg/kg) decreased choice when the probabilities increased. These results show that the GluN2B is a mediator of impulsive/risky choice, but the effects of GluN2B antagonists are dependent on the order in which delays/probabilities are presented. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

摘要

最近研究了N-甲基-D-天冬氨酸受体(NMDA受体)的GluN2B亚基对冲动性的影响。Ro 63-1908是一种对GluN2B具有高度选择性的拮抗剂,它能减少冲动性选择。由于在折扣程序中呈现延迟的顺序会调节药物效应,因此本研究的一个目标是确定Ro 63-1908在延迟折扣程序中的作用,在该程序中,获得大强化物的延迟在整个实验过程中要么增加要么减少。我们还确定了Ro 63-1908在使用升序/降序时间表的概率折扣程序中是否会不同程度地改变风险选择。雄性大鼠接受延迟(n = 24)或概率(n = 24)折扣训练,其中强化延迟/不利几率以升序或降序呈现(每种时间表各n = 12)。训练后,大鼠接受GluN2B拮抗剂Ro 63-1908(0 - 1.0 mg/kg)和CP-101,606(0 - 3.0 mg/kg)。在延迟折扣中,Ro 63-1908(1.0 mg/kg)而非CP-101,606减少了对大强化物的选择,但仅在整个实验过程中延迟减少时才会出现这种情况。在概率折扣中,当获得该备选方案的概率在整个实验过程中降低时,Ro 63-1908(0.3 mg/kg)/CP-101,606(1.0 mg/kg)增加了对大强化物的选择,但当概率增加时,Ro 63-1908(1.0 mg/kg)/CP-101,606(3.0 mg/kg)则减少了选择。这些结果表明,GluN2B是冲动性/风险选择的调节因子,但GluN2B拮抗剂的作用取决于延迟/概率呈现的顺序。(PsycINFO数据库记录(c)2018美国心理学会,保留所有权利)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa49/6283694/4b51616d7ea7/nihms-990530-f0001.jpg

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