Neuropharmacological studies of habitual alcohol drinking behavior in animal models

• Project/Area Number: 17390203
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Kyoto 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: ¥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)
• Keywords: uncoupling 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.

Research Products

• [Journal Article] Early alcohol onset influences on the late alcohol drinking behavior (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Serotonergic mediation of the antidepressant-like of the green leaves odor in mice (2008)
  • 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
• [Journal Article] Reconstruction of dopaminegic neural network and locomotion function in planarian regeneration (2007)
  • 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
• [Journal Article] Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administraion of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone (2007)
  • 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
• [Journal Article] Identification and distribution of typtophan hydroxylase (TPH)-positive neurons in the planarian Dugesia japonica (2007)
  • 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
• [Journal Article] Early alcohol onset influences on the late alcohol drinking behavio in female C57BL mice (2007)
  • 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
• [Journal Article] Reconstraction of dopaminergic neural network and locomotion... (2007)
  • Author(s): Nishimura K, et. al.
  • Journal Title: Develop. Neurobiol. 67 Pages: 1059-1078
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Acupuncture stimulates the release of serotonin, but not dopamine, in the rat nucleus accumbens (2006)
  • 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
• [Journal Article] In vivo brain microdialysis studies on the striatal dopamine and serotonin release in zitter mutant rats (2006)
  • 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
• [Journal Article] PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons In Parkinson's disease rat model (2006)
  • 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
• [Journal Article] Relationship between limbic and cortical 5-HT neurotransmission and acuisition and reversal learning in a go/no-go task in rats (2006)
  • 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
• [Journal Article] Improvement of focal ischemia-induced rat dopaminergic dysfunction by striatal transplantation of mouse embryonic stem cells (2006)
  • 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
• [Journal Article] Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its alteration in 6-hydroxydopamine-treated hemiparkinsonian rat brain (2006)
  • 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
• [Journal Article] Acupuncture stimulates the release of serotonin, but not Dopamine, in the rat nucleus accumbens (2006)
  • Author(s): Yoshimoto K et al.
  • Journal Title: Tohoku J Exp Med 208 Pages: 321-326
  • NAID: 10017969062
• [Journal Article] In vivo brain microdialysis studies on the striatal dopamine And serotonin release in zitter mutant rat (2006)
  • Author(s): Yoshimoto K et al.
  • Journal Title: ech Ageing Dev 127 Pages: 628-632
• [Journal Article] PARK 7 DJ-1 protects degeneration of nigral dopaminergic neurons In Parkinson' s disease rat model (2006)
  • Author(s): Inden M et al.
  • Journal Title: Neurobiol Dis 24 Pages: 144-158
• [Journal Article] Relationship between limbic and cortical 5-HT neurotransmitter And acuisition and reversal learning in go/on task (2006)
  • Author(s): Masaki D et al.
  • Journal Title: Psychopharmacology 189 Pages: 249-258
• [Journal Article] Improvement of focal ischemia-induced rat dopaminergic dysfunction by striatal transplantation (2006)
  • Author(s): Yangisawa D et al.
  • Journal Title: Neurosci Lett 407 Pages: 74-79
• [Journal Article] Distribution of DJ-1, Parkinson' s disease-related protein PARK7 (2006)
  • Author(s): Yanagida T et al.
  • Journal Title: J Pharmacol Sci 102 Pages: 243-247
• [Journal Article] Increase of cadiotrophin-1 immunoreactivity in regenerating and overloaded but not denervated muscle of rats (2005)
  • 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
• [Journal Article] Effect of ultrasonic stimulation on mRNA abundance of uncoupling protein (UCP)2 and UCP3 in gastrocnemius muscle of rats (2005)
  • 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
• [Journal Article] Degeneration of monoaminergic fibers in the aged micrencephalic rat (2005)
  • 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
• [Journal Article] Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning (2005)
  • 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
• [Journal Article] Transplantation of mouse embryonic stem cell-deriv neurons into the striatum, subthalamic nucleus and substantia nigra, and behavioral recovery in hemiparkinsonian rats (2005)
  • 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
• [Journal Article] Effect of moxibution on dopaminergic and serotonergic system of rat nucleus accumbens (2005)
  • 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
• [Journal Article] Increase of cardiotrophin-1 in regenerating rats... (2005)
  • Author(s): Nishikawa J.et al.
  • Journal Title: Neuropathology 25 Pages: 54-65
• [Journal Article] Effect of ultrasonic stimulation on mRNA abundance (2005)
  • Author(s): Kogure A.et al.
  • Journal Title: Clin.Exp.Pharmacol.Physiol. 32(1-2) Pages: 91-93
• [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
• [Journal Article] Transplantation of mouse embryonic stem cell... (2005)
  • Author(s): Inden M.et al.
  • Journal Title: Neuroscience Letter 387 Pages: 151-156
• [Journal Article] Effect of moxibution on dopaminergic and serotonergic (2005)
  • Author(s): Fukuda F.et al.
  • Journal Title: Neurochem.Res. 30(12) Pages: 1607-1613
• [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