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Noradrenergic contributions to cue-driven risk-taking and impulsivity
Psychopharmacology ( IF 3.4 ) Pub Date : 2021-03-02 , DOI: 10.1007/s00213-021-05806-x
Chloe S Chernoff 1 , Tristan J Hynes 1 , Catharine A Winstanley 1
Affiliation  

Rationale

The flashing lights and sounds of modern casinos are alluring and may contribute to the addictive nature of gambling. Such cues can have a profound impact on the noradrenaline (NA) system, which could therefore be a viable therapeutic target for gambling disorder (GD). While there is substantial evidence to support the involvement of NA in the impulsive symptoms of GD, its function in mediating the “pro-addictive” impact of cues is less understood.

Objective

We wished to investigate the role of NA in our rodent assay of decision making and impulsivity, the cued rat gambling task (crGT). Given that sex differences are prominent in addiction disorders, and increasingly reported in the monoaminergic regulation of behaviour, we also prioritised evaluating noradrenergic drugs in both sexes.

Methods

Female and male rats were trained to stability on the crGT and then given intraperitoneal injections of the noradrenaline reuptake inhibitor atomoxetine, the α2A receptor agonist guanfacine, the beta receptor antagonist propranolol, and the α2 receptor antagonist yohimbine.

Results

Atomoxetine dose-dependently improved decision-making score. Guanfacine selectively enhanced decision making in risk-preferring males and optimal performing females. Propranolol and yohimbine did not influence decision making. Atomoxetine and guanfacine reduced premature responses, while yohimbine bi-phasically affected this index of motor impulsivity.

Conclusions

These results support the hypothesis that NA is an important neuromodulator of the cue-induced deficits in decision making observed in laboratory-based gambling paradigms, and suggest that NAergic drugs like atomoxetine and guanfacine may be useful in treating GD.



中文翻译:

Noradrergyc对提示驱动的冒险和冲动的贡献

基本原理

现代赌场的闪光灯和声音诱人,可能助长了赌博的成瘾性。这些提示可能会对去甲肾上腺素(NA)系统产生深远影响,因此可以成为赌博性疾病(GD)的可行治疗靶标。尽管有充分的证据支持NA参与GD的冲动性症状,但其在介导提示的“促成瘾性”影响中的作用还鲜为人知。

客观的

我们希望研究NA在我们的啮齿类动物决策和冲动实验中的作用,这是提示老鼠赌博的任务(crGT)。鉴于成瘾障碍中的性别差异非常明显,并且在单胺能行为规范中越来越多地报道,因此我们也优先评估了两种性别中的去甲肾上腺素能药物。

方法

雌性和雄性大鼠被训练在crGT稳定性,然后给出的去甲肾上腺素再摄取抑制剂阿托莫西汀腹膜内注射时,α 2A受体激动剂胍法辛,β受体拮抗剂普萘洛尔,和α 2受体拮抗剂的育亨宾。

结果

Atomoxetine剂量依赖性地改善了决策得分。胍法辛选择性地增强了偏爱风险较高的男性和表现最佳的女性的决策能力。普萘洛尔和育亨宾不影响决策。托莫西汀和胍法辛可降低过早反应,而育亨宾则双相影响该运动冲动指数。

结论

这些结果支持以下假设:NA是在以实验室为基础的赌博范例中观察到的决策中提示引起的提示缺陷的重要神经调节剂,并表明NAergic药物(如托莫西汀和胍法辛)可能可用于治疗GD。

更新日期:2021-03-02
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