Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT, USA.
Psychopharmacology (Berl). 2014 Oct;231(20):3941-52. doi: 10.1007/s00213-014-3529-y. Epub 2014 Mar 20.
Stress-induced disruption of decision making has been hypothesized to contribute to drug-seeking behaviors and addiction. Noradrenergic signaling plays a central role in mediating stress responses. However, the effects of acute stress on decision making, and the role of noradrenergic signaling in regulating these effects, have not been well characterized.
To characterize changes in decision making caused by acute pharmacological stress, the effects of yohimbine (an α2-adrenergic antagonist) were examined in a delay discounting task. Noradrenergic contributions to decision making were further characterized by examining the effects of propranolol (a β antagonist), prazosin (an α1 antagonist), and guanfacine (an α2 agonist).
Sprague-Dawley rats were administered drugs prior to performance on a delay discounting task, in which the delay preceding the large reward increased within each session (ascending delays). To dissociate drug-induced changes in delay sensitivity from behavioral inflexibility, drug effects were subsequently tested in a modified version of the discounting task, in which the delay preceding the large reward decreased within each session (descending delays).
Yohimbine increased choice of the large reward when tested with ascending delays but decreased choice of the same large reward when tested with descending delays, suggesting that drug effects could be attributed to perseverative choice of the lever preferred at the beginning of the session. Propranolol increased choice of the large reward when tested with ascending delays. Prazosin and guanfacine had no effect on reward choice.
The stress-like effects of yohimbine administration may impair decision making by causing inflexible, perseverative behavior.
应激导致的决策中断被假设为导致觅药行为和成瘾的原因。去甲肾上腺素能信号在介导应激反应中起着核心作用。然而,急性应激对决策的影响,以及去甲肾上腺素能信号在调节这些影响中的作用,尚未得到很好的描述。
为了描述急性药理学应激引起的决策变化,本文在延迟折扣任务中研究了育亨宾(一种 α2-肾上腺素能拮抗剂)的作用。通过检查普萘洛尔(一种β拮抗剂)、哌唑嗪(一种α1 拮抗剂)和胍法辛(一种α2 激动剂)的作用,进一步研究了去甲肾上腺素能对决策的影响。
在进行延迟折扣任务之前,给予 Sprague-Dawley 大鼠药物治疗,在该任务中,每个会话中,大奖励之前的延迟时间都会增加(递增延迟)。为了将药物引起的延迟敏感性变化与行为灵活性降低区分开来,随后在折扣任务的修改版本中测试药物的作用,在该任务中,每个会话中,大奖励之前的延迟时间都会减少(递减延迟)。
育亨宾在递增延迟测试中增加了对大奖励的选择,但在递减延迟测试中减少了对相同大奖励的选择,这表明药物的作用可以归因于在会话开始时对优先选择的杠杆的持续选择。普萘洛尔在递增延迟测试中增加了对大奖励的选择。哌唑嗪和胍法辛对奖励选择没有影响。
育亨宾给药的应激样效应可能通过引起不灵活、持续的行为来损害决策能力。