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1993 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number 04671346
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionToyama Medical and Pharmaceutical University

Principal Investigator

MATSUMOTO Kinzo  Toyama Medical & Pharmaceutical University Reseach Institute for Wakan-Yaku, associate professor, 和漢薬研究所, 助教授 (10114654)

Co-Investigator(Kenkyū-buntansha) OHTA Hiroyuki  Toyama Medical & Pharmaceutical University Reseach Institute for Wakan-Yaku, ass, 和漢薬研究所, 助手 (20211104)
Project Period (FY) 1992 – 1993
KeywordsSocial isolation / Mice / Noradrenaline / Antidepressants / Aggressive behavior / alpha2-Adrenoceptor / beta2-Adrenoceptor / REM sleep deprivation
Research Abstract

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

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Cai Bing: "Biphasic effects of typical antidepressants and mianserin,an atypical antidepressant,on aggressive behavior in socially isolated mice." Pharmacol.Biochem.Behav.44. 519-525 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Cai B., Matsumoto K., Ohta H.and Watanabe H.: "Biphasic effects of typical antideprressants and mianserin, an atypical antidepressant, on aggressive behavior in socially isolated mice" Pharmacol.Biochem.Behav.44. 519-525 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsumoto K., Ojima K., Ohta H.and Watanabe H.: "beta2- but not beta1-adrenoceptors are involved in desipramine enhancement of aggressive behavior in long-term isolated mice." Pharmacol.Biochem.Behav.in press. (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1995-03-27  

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