Hrelja Kelly M, Kawkab Carol, Avramidis Dimitrios K, Ramaiah Shrishti, Winstanley Catharine A
Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
Psychopharmacology (Berl). 2025 Jan;242(1):173-187. doi: 10.1007/s00213-024-06659-w. Epub 2024 Jul 30.
The use of illicit opioids has arguably never been more risky; street drug potency can be dangerously high, is often unknown to the consumer, and results in multiple daily fatalities worldwide. Furthermore, substance use disorder (SUD) is associated with increased maladaptive, risky decisions in laboratory-based gambling tasks. Animal studies can help determine whether this decision-making deficit is a cause or consequence of drug use. However, most experiments have only assessed psychostimulant drugs.
To assess differences in decision-making strategies both before, during, and after self-administration of fentanyl in male and female Long Evans rats.
Male and female Long Evans rats were trained to perform the rat gambling task (rGT), loosely based on the Iowa Gambling Task (IGT) used clinically, and/or self-administer fentanyl. We used the cued version of the rGT, in which sound and light stimuli signal sugar pellet rewards, as cocaine self-administration has the greatest effects on decision making in this task variant.
After training on the cued rGT, female rats self-administered fentanyl more readily, an effect that was most apparent in optimal decision-makers. Contrary to previous reports using cocaine self-administration, decision-making was unaffected during fentanyl self-administration training in either sex. However, risky decision-making increased throughout forced abstinence from fentanyl in males.
These findings complement those from human subjects, in whom preference for uncertain outcomes increased before relapse. These data highlight an abstinence-induced change in cognition that is unique to opiates as compared to psychostimulants, and which may critically contribute to the maintenance of addiction and relapse.
使用非法阿片类药物的风险可能从未如此之高;街头毒品的效力可能高到危险程度,使用者往往并不知晓,且在全球范围内每天都导致多起死亡。此外,物质使用障碍(SUD)与在基于实验室的赌博任务中增加的适应不良、冒险决策有关。动物研究有助于确定这种决策缺陷是药物使用的原因还是后果。然而,大多数实验仅评估了精神刺激药物。
评估雄性和雌性朗·埃文斯大鼠在自我注射芬太尼之前、期间和之后决策策略的差异。
雄性和雌性朗·埃文斯大鼠接受训练以执行大鼠赌博任务(rGT),该任务大致基于临床上使用的爱荷华赌博任务(IGT),和/或自我注射芬太尼。我们使用了rGT的线索版本,其中声音和光刺激表示糖丸奖励,因为可卡因自我给药对该任务变体中的决策有最大影响。
在对线索rGT进行训练后,雌性大鼠更愿意自我注射芬太尼,这种效应在最佳决策者中最为明显。与先前使用可卡因自我给药的报告相反,在芬太尼自我给药训练期间,两性的决策均未受到影响。然而,在雄性大鼠强制戒断芬太尼的整个过程中,冒险决策增加。
这些发现补充了来自人类受试者的研究结果,在人类中,复发前对不确定结果的偏好增加。这些数据突出了与精神刺激药物相比,阿片类药物特有的戒断诱导的认知变化,这可能对成瘾的维持和复发起关键作用。