Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
Psychopharmacology (Berl). 2012 Dec;224(4):489-99. doi: 10.1007/s00213-012-2777-y. Epub 2012 Jul 4.
Alterations in cost-benefit decision making accompany numerous neuropsychiatric conditions, including schizophrenia, attention deficit hyperactivity disorder, and addiction. Central cholinergic systems have been linked to the etiology and/or treatment of many of these conditions, but little is known about the role of cholinergic signaling in cost-benefit decision making.
The goal of these experiments was to determine how cholinergic signaling is involved in cost-benefit decision making, using a behavioral pharmacological approach.
Male Long-Evans rats were trained in either "probability discounting" or "delay discounting" tasks, in which rats made discrete-trial choices between a small food reward and a large food reward associated with either varying probabilities of omission or varying delays to delivery, respectively. The effects of acute administration of different doses of nicotinic and muscarinic acetylcholine receptor agonists and antagonists were assessed in each task.
In the probability discounting task, acute nicotine administration (1.0 mg/kg) significantly increased choice of the large risky reward, and control experiments suggested that this was due to robust nicotine-induced impairments in behavioral flexibility. In the delay discounting task, the muscarinic antagonists scopolamine (0.03, 0.1, and 0.3 mg/kg) and atropine (0.3 mg/kg) both significantly increased choice of the small immediate reward. Neither mecamylamine nor oxotremorine produced reliable effects on either of the decision making tasks.
These data suggest that cholinergic receptors play multiple roles in decision making contexts which include consideration of reward delay or probability. These roles should be considered when targeting these receptors for therapeutic purposes.
成本效益决策的改变伴随着许多神经精神疾病,包括精神分裂症、注意缺陷多动障碍和成瘾。中枢胆碱能系统与许多这些疾病的病因和/或治疗有关,但关于胆碱能信号在成本效益决策中的作用知之甚少。
这些实验的目的是使用行为药理学方法确定胆碱能信号在成本效益决策中的作用。
雄性长耳大仓鼠在“概率折扣”或“延迟折扣”任务中接受训练,在这两种任务中,仓鼠在小食物奖励和大食物奖励之间进行离散试验选择,分别与不同的缺失概率或不同的延迟交付相关。评估了不同剂量的烟碱和毒蕈碱乙酰胆碱受体激动剂和拮抗剂在每种任务中的作用。
在概率折扣任务中,急性尼古丁给药(1.0 mg/kg)显著增加了对大风险奖励的选择,而对照实验表明,这是由于尼古丁引起的行为灵活性严重受损所致。在延迟折扣任务中,毒蕈碱拮抗剂东莨菪碱(0.03、0.1 和 0.3 mg/kg)和阿托品(0.3 mg/kg)均显著增加了对小即时奖励的选择。美加明或 Oxotremorine 均未对任何一种决策任务产生可靠的影响。
这些数据表明,胆碱能受体在包括考虑奖励延迟或概率的决策情境中发挥多种作用。在针对这些受体进行治疗时,应考虑这些作用。