Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Westbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Psychopharmacology (Berl). 2019 Jun;236(6):1901-1915. doi: 10.1007/s00213-019-5173-z. Epub 2019 Jan 31.
Chronic administration of D receptor agonists ropinirole or pramipexole can increase the choice of uncertain rewards in rats, theoretically approximating iatrogenic gambling disorder (iGD).
We aimed to assess the effect of chronic ropinirole in animal models that attempt to capture critical aspects of commercial gambling, including the risk of losing rather than failing to gain, and the use of win-paired sensory stimuli heavily featured in electronic gambling machines (EGMs).
Male Long-Evans rats learned the rat gambling task (rGT; n = 24), in which animals sample between four options that differ in the magnitude and probability of rewards and time-out punishments. In the cued rGT (n = 40), reward-concurrent audiovisual cues were added that scaled in complexity with win size. Rats were then implanted with an osmotic pump delivering ropinirole (5 mg/kg/day) or saline for 28 days.
Chronic ropinirole did not unequivocally increase preference for more uncertain outcomes in either the cued or uncued rGT. Ropinirole transiently increased premature responses, a measure of motor impulsivity, and this change was larger and more long-lasting in the cued task.
These data suggest that explicitly signaling loss prevents the increase in preference for uncertain rewards caused by D receptor agonists observed previously. The ability of win-paired cues to amplify ropinirole-induced increases in motor impulsivity may explain why compulsive use of EGMs is particularly common in iGD. These data offer valuable insight into the cognitive-behavioral mechanisms through which chronic dopamine agonist treatments may induce iGD and related impulse control disorders.
慢性给予 D 受体激动剂罗匹尼罗或普拉克索可增加大鼠对不确定奖赏的选择,理论上近似于医源性赌博障碍(iGD)。
我们旨在评估慢性罗匹尼罗在试图捕捉商业赌博关键方面的动物模型中的作用,包括失去而非未获得的风险,以及在电子赌博机(EGM)中大量使用与赢配对的感觉刺激。
雄性长耳大仓鼠学会了大鼠赌博任务(rGT;n=24),其中动物在四个选项之间进行抽样,这些选项在奖赏和超时惩罚的大小和概率上有所不同。在提示 rGT 中(n=40),增加了与奖赏大小成比例的奖励伴随视听线索。然后,大鼠被植入一个持续输注罗匹尼罗(5mg/kg/天)或盐水的渗透泵,持续 28 天。
慢性罗匹尼罗并未在提示或非提示 rGT 中明确增加对更不确定结果的偏好。罗匹尼罗短暂增加了过早反应,这是一种冲动性的衡量标准,而在提示任务中,这种变化更大且更持久。
这些数据表明,明确提示损失可防止先前观察到的 D 受体激动剂引起的对不确定奖赏的偏好增加。与赢配对的线索增强罗匹尼罗诱导的运动冲动性增加的能力可能解释了为什么 EGM 的强制性使用在 iGD 中尤为常见。这些数据为慢性多巴胺激动剂治疗可能引起 iGD 和相关冲动控制障碍的认知行为机制提供了有价值的见解。