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Neuropharmacological studies of habitual alcohol drinking behavior in animal models

Research Project

Project/Area Number 17390203
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

YOSHIMOTO Kanii  Kyoto Prefectural University of Medicine, Graduate School of Medicine Department of Legal Medicine, Associate Professor (70111903)

Co-Investigator(Kenkyū-buntansha) YASUHARA Masahiro  Kyoto Prefectural University of Medicine, Department of Legal Medicine, Professor (60305604)
西村 陽  京都府立医科大学, 医学研究科, 講師 (00360040)
横山 ちひろ  京都府立医科大学, 医学研究科, 講師 (90264754)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥8,480,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥5,700,000 (Direct Cost: ¥5,700,000)
Keywordsuncoupling protein / ethanol / RNA / 5-HT receptor / nucleus accumbens / mice / 習慣飲酒 / マウス / 近交系
Research Abstract

Alcohol drinking behavior results from an intricate interplay between genes and environmetal factors, but there remains little understanding of how drinking onset and housing conditions interact to influence on late alcohol drinking behavior. Expression of uncoupling protein-1 (UCP1) in brown adipose tissue (BAT) was studied in young and rats. Mitocondrial UCP1 in BAT is an important key molecule for non-shivering thermogenesis. IP injection of EtOH (2g/kg) caused a decreased expression of BAT UCP1 mRNA in both young and aged rats, but the magnitude of UCP1 mRNA decrease was larger in aged rats than in young rats. Alcohol drinking behavior depends on age of drinking onset and the sensitivity to alcohol associated with functions of ACC DA and 5-HT releases during the process of aging. Mice were injected s.c. with 5, 10 and 20 mg/kg mCPP for 15 days, respectively. Daily intakes of water and 10% ethanol were measured to evaluate alcohol preference (AP) (%) and an alcohol consumption score (g/kg/day).The levels of dopamine (DA) and serotonin (5-H')were analyzed by ECD-HPLC in. the frontal cortex (FC), lateral hypothalamus (LH) and striatum (C/P). MCPP increased AP in a dose-dependently manner. Positive and negative relationships were noted between alcohol consumption score and food intake and mCPP, respectively. MCPP (20mg/kg) increased the level of DA in LH and C/P. The relationship between the levels of 5-HT and mCPP showed a positive correlation in the LH and C/P. The ratios of DOPAC/DA and 5-HIAA/5-HT showed negative correlations with mCPP. It was suggested that the development of alcohol dependence was associated with the down-regulation of 5-HT2c receptor function.
Possible underlying reasons for different alcohol drinking behavior in adults include reduced sensitivity to alcohol in the rewarding system and altered responses of the autonomic nerves associated with 5-HT2 receptor functions, e.g., energy dissipation and the stress of housing conditions.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (33 results)

All 2008 2007 2006 2005

All Journal Article (32 results) (of which Peer Reviewed: 4 results) Presentation (1 results)

  • [Journal Article] Early alcohol onset influences on the late alcohol drinking behavior2008

    • Author(s)
      K.Yoshimoto, et. al.
    • Journal Title

      Trends in Developmental Biology 2

      Pages: 45-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Serotonergic mediation of the antidepressant-like of the green leaves odor in mice2008

    • Author(s)
      Y. Nakatomi, C. Yokoyama, S. Kinoshita, D. Masaki, H. Tsuchida, H. Onoe, K. Yoshimoto, K. Fukui
    • Journal Title

      Neuroscience Letter 436

      Pages: 167-170

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Reconstruction of dopaminegic neural network and locomotion function in planarian regeneration2007

    • Author(s)
      Nishimura, K., Kitamura, Y., Inoue, T., Umesono, Y., Sano, S., Yoshimoto, K., Inden M., Takata, K., Taniguchi, T., Shimohama, S., Agata, K
    • Journal Title

      Develop. Neurobiol 67(8)

      Pages: 1059-1078

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administraion of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone2007

    • Author(s)
      Inden, M., Kitamura, Y., Takeuchi, H., Yanagida, T., Takata, K., Kobayashi, Y., Taniguchi, T., Yoshimoto, K., Kaneko, M., Okuma, Y., Taira, T., Ariga, H
    • Journal Title

      J Neurochem 101(6)

      Pages: 1491-1504

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Identification and distribution of typtophan hydroxylase (TPH)-positive neurons in the planarian Dugesia japonica2007

    • Author(s)
      Nishimura, K., Kitamura, Y., Inoue, T., Umesono, Y., Yoshimoto, K., Takeuchi, K., Taniguchi, T., Agata, K
    • Journal Title

      Neurosci. Res 59

      Pages: 101-106

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Early alcohol onset influences on the late alcohol drinking behavio in female C57BL mice2007

    • Author(s)
      K. Yoshimoto, S. Komura, J. Matsuura, S. Hotta, F. Fukuda, M. Hori
    • Journal Title

      Trends in Developmental Biology 2

      Pages: 45-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Reconstraction of dopaminergic neural network and locomotion...2007

    • Author(s)
      Nishimura K, et. al.
    • Journal Title

      Develop. Neurobiol. 67

      Pages: 1059-1078

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Idetification and distribution of tryptophan positive neuron...2007

    • Author(s)
      Nishimura K, et. al.
    • Journal Title

      Neurosci. Res. 59

      Pages: 101-106

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurodegeneration of mouse nigrostriatal dopaminergic neurons...2007

    • Author(s)
      Inden M, et. al.
    • Journal Title

      J. Neurochem 101

      Pages: 1491-1504

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acupuncture stimulates the release of serotonin, but not dopamine, in the rat nucleus accumbens2006

    • Author(s)
      Yoshimoto, K., Fukuda, F., Hori, M., Kato, B., Kato, H., Hattori, H., Tokuda, N., Kuriyama, K., Yano, T., Yasuhara, M
    • Journal Title

      Tohoku J. Exp. Med 208

      Pages: 321-326

    • NAID

      10017969062

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] In vivo brain microdialysis studies on the striatal dopamine and serotonin release in zitter mutant rats2006

    • Author(s)
      Yoshimoto, K., Nishimura, A., Hattori, H., Joyce, JN., Yoshida, T., Hioki, C., Kogure, A., Ueda, S
    • Journal Title

      Mach Ageing Dev 127

      Pages: 628-632

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons In Parkinson's disease rat model2006

    • Author(s)
      Inden, M., Taira, T., Kitamura, Y., Yanagida, T., Tsuchiya, D., Takata, K., Yanagisawa, D., Nishimura, K., Taniguchi, T., Kiso, Y., Yoshimoto, K., Agatsuma, T., Koide-Yoshida, S., Iguchi-Ariga, SM., Shimohama, S. Ariga, H
    • Journal Title

      Neurobiol Dis 24

      Pages: 144-158

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Relationship between limbic and cortical 5-HT neurotransmission and acuisition and reversal learning in a go/no-go task in rats2006

    • Author(s)
      Masaki, D., Yokoyama, C., Kinoshita, S., Tsuchida, H., Nakatomi, Y., Yoshimoto, K., Fukui, K
    • Journal Title

      Pshchopharmacology 189

      Pages: 249-258

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Improvement of focal ischemia-induced rat dopaminergic dysfunction by striatal transplantation of mouse embryonic stem cells2006

    • Author(s)
      Yanagisawa, D., Qi, M., Kim, D., Kitamura, Y., Inden, M., Tsuchiya, D., Takata, K., Taniguchi, T., Yoshimoto, K., Shimahama, S., Akaike, A., Sumi, S., Inoue, K
    • Journal Title

      Neuroscience Letter 407

      Pages: 74-79

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its alteration in 6-hydroxydopamine-treated hemiparkinsonian rat brain2006

    • Author(s)
      Yanagida, T., Takata, K., Inden, M., Kitamura, Y., Taniguchi, T., Yoshimto, K., Taira, T., Ariga, H
    • Journal Title

      J Pharmacol Sci 102

      Pages: 243-247

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Acupuncture stimulates the release of serotonin, but not Dopamine, in the rat nucleus accumbens2006

    • Author(s)
      Yoshimoto K et al.
    • Journal Title

      Tohoku J Exp Med 208

      Pages: 321-326

    • NAID

      10017969062

    • Related Report
      2006 Annual Research Report
  • [Journal Article] In vivo brain microdialysis studies on the striatal dopamine And serotonin release in zitter mutant rat2006

    • Author(s)
      Yoshimoto K et al.
    • Journal Title

      ech Ageing Dev 127

      Pages: 628-632

    • Related Report
      2006 Annual Research Report
  • [Journal Article] PARK 7 DJ-1 protects degeneration of nigral dopaminergic neurons In Parkinson' s disease rat model2006

    • Author(s)
      Inden M et al.
    • Journal Title

      Neurobiol Dis 24

      Pages: 144-158

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Relationship between limbic and cortical 5-HT neurotransmitter And acuisition and reversal learning in go/on task2006

    • Author(s)
      Masaki D et al.
    • Journal Title

      Psychopharmacology 189

      Pages: 249-258

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Improvement of focal ischemia-induced rat dopaminergic dysfunction by striatal transplantation2006

    • Author(s)
      Yangisawa D et al.
    • Journal Title

      Neurosci Lett 407

      Pages: 74-79

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distribution of DJ-1, Parkinson' s disease-related protein PARK72006

    • Author(s)
      Yanagida T et al.
    • Journal Title

      J Pharmacol Sci 102

      Pages: 243-247

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increase of cadiotrophin-1 immunoreactivity in regenerating and overloaded but not denervated muscle of rats2005

    • Author(s)
      J. Nishikawa, K. Sakuma, Y. Sorimachi, Yoshimoto, K. M. Yasuhara
    • Journal Title

      Neuropathology 25

      Pages: 54-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of ultrasonic stimulation on mRNA abundance of uncoupling protein (UCP)2 and UCP3 in gastrocnemius muscle of rats2005

    • Author(s)
      A. Kogure, T. Yoshida, Y. Takakura, T. Umekawa, C. Hioki, K. Yoshioka, Yoshimoto, K. T. Yoshikawa
    • Journal Title

      Clin Exp Pharmacol Physiol 32(1-2)

      Pages: 91-93

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Degeneration of monoaminergic fibers in the aged micrencephalic rat2005

    • Author(s)
      Watabe, Y. Yoshimoto, K., Eguchi, M., Ueda, S
    • Journal Title

      Neuroscience letter 385

      Pages: 82-86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning2005

    • Author(s)
      Ueda, S., Sakakibara, S., Yoshimoto, K
    • Journal Title

      Neuroscience 135

      Pages: 395-402

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Transplantation of mouse embryonic stem cell-deriv neurons into the striatum, subthalamic nucleus and substantia nigra, and behavioral recovery in hemiparkinsonian rats2005

    • Author(s)
      Inden, M., Kim, DH., Qi, M., Kitamura, Y., Yanagisawa, D., Nishimura, K., Tsuchia, D., Takata, K., Hayashi, K., Taniguchi, T., Yoshimoto, K., Shimohama, S., Sumi, S., Inoue, K
    • Journal Title

      Nurosci Lett 387

      Pages: 151-156

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of moxibution on dopaminergic and serotonergic system of rat nucleus accumbens2005

    • Author(s)
      Fukuda, F., Shinbara, H., Yoshimoto, K., Yana, T., Kuriyama, K
    • Journal Title

      Neurochem Res 30(12)

      Pages: 1607-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increase of cardiotrophin-1 in regenerating rats...2005

    • Author(s)
      Nishikawa J.et al.
    • Journal Title

      Neuropathology 25

      Pages: 54-65

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of ultrasonic stimulation on mRNA abundance2005

    • Author(s)
      Kogure A.et al.
    • Journal Title

      Clin.Exp.Pharmacol.Physiol. 32(1-2)

      Pages: 91-93

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Degeneration of monoaminergic fibers in aged..2005

    • Author(s)
      Watabe Y, Yoshimoto K et al.
    • Journal Title

      Neuroscience Letter 385

      Pages: 82-86

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transplantation of mouse embryonic stem cell...2005

    • Author(s)
      Inden M.et al.
    • Journal Title

      Neuroscience Letter 387

      Pages: 151-156

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of moxibution on dopaminergic and serotonergic2005

    • Author(s)
      Fukuda F.et al.
    • Journal Title

      Neurochem.Res. 30(12)

      Pages: 1607-1613

    • Related Report
      2005 Annual Research Report
  • [Presentation] アルコールと飲酒行動 - アルコール投与による血中グレリン変化2007

    • Author(s)
      吉本寛司, 他
    • Organizer
      第42回 日本アルコール・薬物医学会
    • Place of Presentation
      大津
    • Related Report
      2007 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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