Study on social isolation-induced functional changes in noradrenergic system in the brain

社会隔离引起的大脑去甲肾上腺素能系统功能变化的研究

• 批准号: 04671346
• 负责人: MATSUMOTO Kinzo
• 金额: $ 1.34万
• 依托单位: Toyama Medical and Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671346/
• 关键词: Social isolation; Mice; Noradrenaline; Antidepressants; Aggressive behavior; alpha2-Adrenoceptor; beta2-Adrenoceptor; REM sleep deprivation; Social Isolation; α2-adrenoceptor; β2-adrenoceptor; noradrenaline; Anticlepressants; DSP-4

Long-term social isolation enhances spontaneous motor activity, and induces aggressive behavior in mice and rats. However, underlying mechanisms of such behavioral changes remain unclear. We preliminary reported that an antidepressant drug desipramine (DMI) enhanced aggressive behavior in isolated mice (Matsumoto et al., Pharmacol.Biochem.Behav., 39, 167, 1991). In this study, we investigated functional changes in central noradrenergic system caused by social isolation. Male ddY mice were isolated for 6-7 weeks before experiments. When testing aggressive, two isolated mice were placed in a neutral cage. The total duration of biting attacks and/or wrestling observed during a 20-min period was measured. Antidepressants with ability to block noradrenaline (NA) uptake in the brain enhanced aggressive behavior at lower doses. The effects of these drugs were blockd by an a2 adrenoceptor antagonist yohimbine, but not alpha1 adrenoceptor antagonist prazosin, suggesting an involvement of alpha2 adrenoceptors in antidepressant enhancement of aggressive behavior. Moreover, a beta-adrenoceptor atntagonist propranolol and a beta2-adrenoceptor antagonist ICIII8551 dose-dependently blockd the effect of DMI without affecting the basal aggressive behavior, while a beta1-adrenoceptor antagonist metprolol failed to affect the effect of desipramine. Clenbuterol, a selective beta2-agonist, enhanced aggressive behavior in isolated mice. Taken together, these results indicated that alpha2- and beta2-adrenoceptor stimulation by NA plays important roles in enhancement of aggressive behavior. Then, we tested effect of a neurotoxin DSP-4 on the aggressive behavior in isolated mice. This toxin is known to selectively degnerate noradrenergic terminals originating from locus coeruleus. DSP-4 treatment did not affect the basal aggressive behavior, but it attenuated the DMI enhancement of aggressive behavior. Thus, these results show the possibility that the activity of locus coeruleus noradrener

长期的社会隔离增强自发运动活动，并诱导小鼠和大鼠的攻击行为。然而，这种行为变化的潜在机制仍不清楚。我们初步报道了抗抑郁药地昔帕明（Desipramine，简称地昔帕明）增强了隔离小鼠的攻击行为（松本等人，药理学.生物化学.行为，39，167，1991）。在本研究中，我们探讨了社会隔离引起的中枢去甲肾上腺素能系统的功能变化。实验前将雄性ddY小鼠分离6-7周。当测试攻击性时，将两只隔离的小鼠置于中性笼中。在20分钟的时间内观察到的咬攻击和/或摔跤的总持续时间进行了测量。具有阻断大脑中去甲肾上腺素（NA）摄取能力的抗抑郁药在较低剂量下增强了攻击性行为。这些药物的作用可被α 2肾上腺素受体拮抗剂育亨宾阻断，但不能被α 1肾上腺素受体拮抗剂哌唑嗪阻断，这表明α 2肾上腺素受体参与抗抑郁剂增强攻击行为。β-肾上腺素能受体拮抗剂普萘洛尔和β_2-肾上腺素能受体拮抗剂ICIII 8551可剂量依赖性地阻断去甲丙咪嗪的作用，但不影响基础攻击行为，而β_1-肾上腺素能受体拮抗剂美托洛尔则不影响去甲丙咪嗪的作用。盐酸克伦特罗，一种选择性β 2受体激动剂，增强了孤立小鼠的攻击行为。综上所述，这些结果表明NA刺激α 2和β 2肾上腺素受体在增强攻击行为中起重要作用。然后，我们测试了神经毒素DSP-4对隔离小鼠攻击行为的影响。已知该毒素可选择性地降解源自蓝斑的去甲肾上腺素能末梢。DSP-4处理不影响基础攻击行为，但减弱了攻击行为的持续增强。因此，这些结果表明，蓝斑去甲肾上腺素的活动可能

项目成果

Asakura Wataru: "Effect of α2 adrenergic drugs on REM sleep deprivation-induced increase in swimming activity in the forced swimming test." Pharmacol.Biochem.Behav.46. 111-115 (1993)

Asakura Wataru：“在强迫游泳测试中，α2 肾上腺素能药物对 REM 睡眠剥夺引起的游泳活动增加的影响。”111-115（1993）。

Asakura, W., Matsumoto K., Ohta H.and Watanabe H.: "Effect of alph2-adrenergic drugs on REM sleep deprivation-induced increase inswimming activity" Pharmacol.Biochem.Behav.46. 111-115 (1993)

Asakura, W.、Matsumoto K.、Ohta H. 和 Watanabe H.：“α2 肾上腺素药物对快速眼动睡眠剥夺引起的游泳活动增加的影响”Pharmacol.Biochem.Behav.46。

Matsumoto Kinzo: "β2-but not β1-adrenoceptors are involved in desipramine enhancement of aggressive behavior in long-term isolated mice." Pharmacol.Biochem.Behav.(印刷中). (1994)

Kinzo Matsumoto：“β2-而非 β1-肾上腺素受体参与地昔帕明增强长期隔离小鼠的攻击行为。”（正在出版）。

Asakura Wataru: "REM sleep deprivation potentiates the effects of imipramine and desipramine but not that of clomipramine in the forced swimming test." Japan.J.Pharmacol.63. 455-460 (1993)

Asakura Wataru：“在强迫游泳测试中，快速眼动睡眠剥夺会增强丙咪嗪和地昔帕明的作用，但不会增强氯米帕明的作用。”

Asakura, W., Matsumoto K., Ohta H.and Watanabe H.: "REM sleep deprivation potentated the effects of imipramine and desipramine but not that of clomipramine in the forced swimming test." Japan.J.Pharmacol.63. 455-460 (1993)

Asakura, W.、Matsumoto K.、Ohta H. 和 Watanabe H.：“在强迫游泳测试中，快速眼动睡眠剥夺增强了丙咪嗪和地昔帕明的作用，但不增强氯米帕明的作用。”