Schippers M C, Schetters D, De Vries T J, Pattij T
Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Psychopharmacology (Berl). 2016 Jul;233(14):2775-85. doi: 10.1007/s00213-016-4337-3. Epub 2016 Jun 1.
High levels of impulsivity have been associated with psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and substance abuse. In addition, acute stress is known to exacerbate many psychiatric symptoms in impulse control disorders.
The purpose of the current study was to investigate the acute effects of the pharmacological stressor yohimbine on response inhibition and impulsive choice.
A group of male rats (n = 12) was trained in the delayed reward task (DRT) to assess impulsive choice. A separate group (n = 10) was trained in the stop-signal task (SST) to measure response inhibition. Upon stable responding, the effects of yohimbine (0, 1.25, 2.5, and 5 mg/kg i.p.) were tested in a Latin square design.
Acute yohimbine significantly increased the preference for the large and delayed reinforcer in the DRT, indicating a decrease in impulsive choice. On the contrary, the effect size of 1.25 mg/kg yohimbine on stop-signal reaction times correlated negatively with baseline performance, suggesting a baseline-dependent effect on response inhibition as measured in the SST.
The current data suggest that the effects of the pharmacological stressor yohimbine on impulse control strongly depend on the type of impulsive behavior. Pharmacological stress decreased impulsive decision making, an observation that is in line with previously published rodent studies. By contrast, the lowest dose of yohimbine revealed a baseline-dependent effect on response inhibition. As such, the effects of yohimbine are largely comparable to the effects of psychostimulants on impulsivity and may support the notion of cross sensitization of stress and psychostimulants.
高冲动性与注意力缺陷多动障碍(ADHD)和药物滥用等精神疾病有关。此外,已知急性应激会加剧冲动控制障碍中的许多精神症状。
本研究的目的是调查药理应激源育亨宾对反应抑制和冲动选择的急性影响。
一组雄性大鼠(n = 12)接受延迟奖励任务(DRT)训练以评估冲动选择。另一组(n = 10)接受停止信号任务(SST)训练以测量反应抑制。在反应稳定后,采用拉丁方设计测试育亨宾(0、1.25、2.5和5mg/kg腹腔注射)的效果。
急性给予育亨宾显著增加了DRT中对大的和延迟强化物的偏好,表明冲动选择减少。相反,1.25mg/kg育亨宾对停止信号反应时间的效应大小与基线表现呈负相关,表明在SST中测量的对反应抑制有基线依赖性效应。
目前的数据表明,药理应激源育亨宾对冲动控制的影响强烈依赖于冲动行为的类型。药理应激降低了冲动决策,这一观察结果与先前发表的啮齿动物研究一致。相比之下,最低剂量的育亨宾对反应抑制显示出基线依赖性效应。因此,育亨宾的作用在很大程度上与精神兴奋剂对冲动性的作用相当,可能支持应激和精神兴奋剂交叉致敏的观点。