Mizoguchi Hiroyuki, Wang Tian, Kusaba Mizuki, Fukumoto Kazuya, Yamada Kiyofumi
Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University, Nagoya, 464-8601, Japan.
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 466-8560, Japan.
Behav Brain Res. 2019 Feb 1;359:935-941. doi: 10.1016/j.bbr.2018.06.016. Epub 2018 Jun 20.
Patients suffering from neuropsychiatric disorders such as substance use and addiction disorders show impaired decision-making, which may be associated with their psychiatric disorders. Previously, using a gambling test for rodents, we demonstrated that methamphetamine-dependent rats showed alterations in their decision-making strategy. In this study, we investigated the effect of nicotine on impaired decision-making strategy in rats which have been treated repeatedly with methamphetamine. Nicotine has previously been shown to have therapeutic effects on attentional and cognitive abnormalities in psychosis. Rats were administered methamphetamine subcutaneously (sc) at 4 mg/kg once a day, for 30 days, and their decision-making was then assessed with a rodent gambling task. We found that methamphetamine-treated rats preferred the high-risk/high-return actions, which is consistent with our previous findings. Methamphetamine-induced impairment of decision-making was reversed by daily nicotine treatment (0.3 mg/kg, sc). This effect was associated with the reduction of lose-shift behavior after negative reward prediction error. Repeated treatment with nicotine had no effects on arm-choice behavior in naïve rats. Varenicline, an α4β2-nicotinic acetylcholine receptor partial agonist, also ameliorated the altered decision-making in methamphetamine-treated rats. Our findings suggest that nicotine treatment is useful for ameliorating the altered decision-making caused by methamphetamine treatment, and that the α4β2-nicotinic acetylcholine receptor is a therapeutic target for poor decision-making.
患有神经精神疾病（如物质使用和成瘾障碍）的患者表现出决策能力受损，这可能与他们的精神疾病有关。此前，我们通过对啮齿动物进行赌博测试，证明了甲基苯丙胺依赖的大鼠在决策策略上存在改变。在本研究中，我们调查了尼古丁对反复接受甲基苯丙胺治疗的大鼠决策策略受损的影响。此前已表明尼古丁对精神病患者的注意力和认知异常具有治疗作用。大鼠每天皮下注射（sc）4mg/kg甲基苯丙胺，持续30天，然后用啮齿动物赌博任务评估它们的决策能力。我们发现，接受甲基苯丙胺治疗的大鼠更喜欢高风险/高回报的行为，这与我们之前的发现一致。每日尼古丁治疗（0.3mg/kg，sc）可逆转甲基苯丙胺引起的决策能力损害。这种作用与负奖励预测误差后损失转移行为的减少有关。尼古丁反复治疗对未接触过药物的大鼠的臂选择行为没有影响。伐尼克兰，一种α4β2烟碱型乙酰胆碱受体部分激动剂，也改善了甲基苯丙胺治疗大鼠的决策改变。我们的研究结果表明，尼古丁治疗有助于改善甲基苯丙胺治疗引起的决策改变，并且α4β2烟碱型乙酰胆碱受体是决策能力差的治疗靶点。
