Zack Martin H, Lobo Daniela S, Biback Candice, Fang Tim, Smart Kelly, Tatone Daniel, Kalia Aditi, Digiacomo Daniel, Kennedy James L
Centre for Addiction and Mental Health, Toronto, Canada.
J Psychopharmacol. 2017 Jan;31(1):31-42. doi: 10.1177/0269881116665329. Epub 2016 Sep 27.
This study investigated the role of dopamine, and specifically the D1 receptor (D1R), in the reinforcing effects of a slot-machine game in healthy volunteers ( n=30). To compare gambling and drug effects, subjects received the prototypic psychostimulant drug d-amphetamine (AMPH; 20 mg) in a multi-session, placebo-controlled design. To isolate D1R, half the subjects were pretreated with the preferential D2 receptor antagonist haloperidol (HAL; 3 mg), and the other half with the mixed D1-D2 antagonist fluphenazine (FLU; 3 mg) before the game (Phase I) and AMPH (Phase II). HAL decreased and FLU increased the post-game desire to gamble and post-AMPH desire to take AMPH again, as well as amphetamine scale ratings on the Addiction Research Center Inventory after gambling and AMPH. The effects of the antagonists on desire to gamble and to take AMPH again were significantly intercorrelated. HAL increased and FLU decreased the salience of negative affective words on a rapid reading task after both reinforcers. HAL also decreased the salience of gambling words after AMPH. Both reinforcers increased diastolic blood pressure equally under antagonists and placebo. Results indicate that D1R plays a parallel role in the psychostimulant-like, incentive-motivational, and salience-enhancing effects of gambling and AMPH. Moderate D1R activation appears to optimize these effects in healthy subjects.
本研究调查了多巴胺，特别是D1受体（D1R）在健康志愿者（n = 30）的老虎机游戏强化效应中的作用。为了比较赌博和药物的效果，受试者在多阶段、安慰剂对照设计中接受了原型精神兴奋剂药物d-苯丙胺（AMPH；20 mg）。为了分离D1R，一半受试者在游戏（第一阶段）和AMPH（第二阶段）前接受了优先D2受体拮抗剂氟哌啶醇（HAL；3 mg）预处理，另一半接受了D1-D2混合拮抗剂氟奋乃静（FLU；3 mg）预处理。HAL降低了，而FLU增加了游戏后再次赌博的欲望以及服用AMPH后再次服用AMPH的欲望，以及赌博和服用AMPH后成瘾研究中心量表上的苯丙胺评分。拮抗剂对赌博欲望和再次服用AMPH欲望的影响显著相互关联。在两种强化物作用后，HAL增加而FLU降低了快速阅读任务中负面情感词汇的显著性。HAL还降低了服用AMPH后赌博词汇的显著性。在拮抗剂和安慰剂作用下，两种强化物对舒张压的升高作用相同。结果表明，D1R在赌博和AMPH的精神兴奋剂样、激励动机和显著性增强效应中发挥着平行作用。适度的D1R激活似乎能在健康受试者中优化这些效应。
