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Role of astrocytes in rewarding effects of drugs of abuse

Research Project

Project/Area Number 17500264
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionHoshi University, School of Pharmacy and pharmaceutical Sciences

Principal Investigator

NARITA Minoru  Hoshi University, School of Pharmacy and pharmaceutical Sciences, Department of toxicology, Associate professor, 薬学部, 助教授 (40318613)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsGlial cell / Psychological dependence / Drug dependence / Astrocyte / Plasticity / Protein kinase C / グルタミン酸受容体 / メタンフェタミン / 中脳辺縁ドパミン神経 / 細胞内Ca^<2+>応答 / Glial fibrially acidic protein
Research Abstract

It is well known that long-term exposure to psychostimulants induces neuronal plasticity. Recently, accumulating evidence suggests that astrocytes may actively participate in synaptic plasticity. In this study, I found that in vitro treatment with cortical neuron/glia co-cultures with either methamphetamine (METH) or morphine (MRP) caused the activation of astrocytes via protein kinase C (PKC). Purified astrocytes were markedly activated by METH, whereas MRP had no such effect. METH, but not MRP, caused a long-lasting astrocytic activation in cortical neuron/glia co-cultures. Treatment with METH enhanced the Ca^<2+> responses to glutamate in cortical neurons. I show here that a glial modulator propentofylline (PPF) dramatically diminished the activation of astrocytes induced by drugs of abuse, such as METH and MRP. Treatment with PPF also suppressed both METH-and MRP-induced rewarding effects. On the other hand, intra-nucleus accumbens (N.Acc.) administration of astrocyte-conditioned medium (ACM) aggravated the development of rewarding effects induced by METH and MRP. Moreover, intra-N.Acc. treatment with ACM collected from METH-treated astrocytes (METH-ACM) significantly and dramatically enhanced the rewarding effect of METH. I also found that some chemokines, such as monocyte chemoattractant protein-5 and soluble tumor necrosis factor receptor-1, were identified in METH-ACM. These findings suggest that astrocytic activation through the stimulation of PKC or astrocyte-related soluble factors could amplify the development of rewarding effect of METH and MRP. The present study provides direct evidence that astrocytes may, at least in part, contribute to the development of rewarding effects induced by psychostimulants and opioids.

Report

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

    (46 results)

All 2007 2006 2005

All Journal Article (46 results)

  • [Journal Article] Involvement of microglia in the ethanol-induced neuropathic pain-like state in the rat.2007

    • Author(s)
      M.Narita, K.Miyoshi, M.Narita, T.Suzuki
    • Journal Title

      Neurosci. Lett. 414

      Pages: 21-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Chronic pain-induced astrocyte activation in the cingulate cortex with no change in neural or glial differentiation from neural stem cells in mice.2007

    • Author(s)
      N.Kuzumaki, M.Narita, M.Narita, N.Hareyama, K.Niikura, Y.Nagumo, H.Nozaki, T.Amano, T.Suzuki
    • Journal Title

      Neurosci. Lett. 415

      Pages: 22-27

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Implication of protein kinase C in the orexin-induced elevation of extracellular dopamine levels and its rewarding effect.2007

    • Author(s)
      M.Narita, Y.Nagumo, M.Miyatake, D.Ikegami, K.Kurahashi, T.Suzuki
    • Journal Title

      Eur. J. Neurosci. 25

      Pages: 1537-1545

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of microglia in the ethanol-induced neuropathic pain-like state in the rat.2007

    • Author(s)
      M.Narita, K.Miyoshi, M.Narita, T.Suzuki
    • Journal Title

      Neurosci.Lett. 414

      Pages: 21-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Chronic pain-induced astrocyte activation in the cingulate cortex with no change in neural or glial differentiation from neural stem cells in mice.2007

    • Author(s)
      N.Kuzumaki, M.Narita, M.Narita, N.Hareyama, K.Niikura, Y.Nagumo, H.Nozaki, T.Amano, T.Suzuki
    • Journal Title

      Neurosci.Lett. 415

      Pages: 22-27

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Implication of protein kinase C in the orexin-induced elevation of extracellular dopamine levels and its rewarding effect.2007

    • Author(s)
      M.Narita, Y.Nagumo, M.Miyatake, D.Ikegami, K.Kurahashi, T.Suzuki
    • Journal Title

      Eur.J.Neurosci. 25

      Pages: 1537-1545

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of microglia in the ethanol-induced neuropathic pain-like state in the rat.2007

    • Author(s)
      Narita M, Miyoshi K, Narita M, Suzuki T
    • Journal Title

      Neurosci.Lett. 414

      Pages: 21-25

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chronic pain-induced astrocyte activation in the cingulate cortex with no change in neural or glial differentiation from neural stem cells in mice.2007

    • Author(s)
      Kuzumaki N, Narita M, Narita M, Harayama N, Niikura K, Nagumo Y, Nozaki H, Amano T, Suzuki T
    • Journal Title

      Neurosci.Lett. 415

      Pages: 22-27

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Implication of protein kinase C in the orexin-induced elevation of extracellular dopamine levels and its rewarding effect.2007

    • Author(s)
      Narita M, Nagumo Y, Miyatake M, Ikegami D, Kurahashi K, Suzuki T
    • Journal Title

      Eur.J.Neurosci. 25

      Pages: 1537-1545

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Direct evidence of astrocytic modulation in the development of rewarding effects induced by drugs of abuse.2006

    • Author(s)
      M.Narita, M.Miyatake, M.Narita, M.Shibasaki, K.Shindo, A.Nakamura, N.Kuzumaki, Y.Nagumo, T.Suzuki
    • Journal Title

      Neuropsychopharmacology 31

      Pages: 2476-2488

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of neuronal NR2B subunit containing NMDA receptor-mediated Ca^<2+> influx and astrocytic activation in cultured mouse cortical neurons and astrocytes.2006

    • Author(s)
      H.Kato, M.Narita, M.Miyatake, Y.Yajima, T.Suzuki
    • Journal Title

      Synapse 59

      Pages: 10-17

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of gap junction in the expression of morphine-induced antinociception.2006

    • Author(s)
      M.Suzuki, M.Narita, A.Nakamura, T.Suzuki
    • Journal Title

      Eur. J. Pharmacol. 535

      Pages: 169-171

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical δ-opioid receptor dysfunction.2006

    • Author(s)
      M.Narita, N.Kuzumaki, M.Narita, C.Kaneko, N.Hareyama, M.Miyatake, K.Shindo, K.Miyoshi, M.Nakajima, Y.Nagumo, F.Sato, H.Wachi, Y.Seyama, T.Suzuki
    • Journal Title

      J. Neurochem. 97

      Pages: 1369-1378

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] μ-Opioid receptor internalization-dependent and -independent mechanisms of the development of tolerance to μ-opioid receptor agonists : comparison between etorphine and morphine.2006

    • Author(s)
      M.Narita, M.Suzuki, M.Narita, K.Niikura, A.Nakamura, M.Miyatake, Y.Yajima, T.Suzuki
    • Journal Title

      Neuroscience 138

      Pages: 609-619

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of δ-opioid receptor function in neurogenesis and neuroprotection.2006

    • Author(s)
      M.Narita, N.Kuzumaki, M.Miyatake, F.Sato, H.Wachi, Y.Seyama, T.Suzuki
    • Journal Title

      J. Neurochem. 97

      Pages: 1494-1505

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] モルヒネ依存における持続的神経内プロテインキナーゼCの活性化と細胞-細胞間相互作用.2006

    • Author(s)
      成田 年, 宮竹真由美, 鈴木雅美, 鈴木 勉
    • Journal Title

      日薬理誌 127

      Pages: 32-35

    • NAID

      10017495082

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 薬物依存形成の分子機構 : 細胞間相互作用とグリア細胞の役割.2006

    • Author(s)
      成田 年, 宮竹真由美, 鈴木雅美, 葛巻直子, 鈴木 勉
    • Journal Title

      日本神経精神薬理学雑誌 26

      Pages: 33-39

    • NAID

      10017328033

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of gap junction in the expression of morphine-induced antinociception.2006

    • Author(s)
      M.Suzuki, M.Narita, A.Nakamura, T.Suzuki
    • Journal Title

      Eur.J.Pharmacol. 535

      Pages: 169-171

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction.2006

    • Author(s)
      M.Narita, N.Kuzumaki, M.Narita, C.Kaneko, N.Hareyama, M.Miyatake, K.Shindo, K.Miyoshi, M.Nakajima, Y.Nagumo, F.Sato, H.Wachi, Y.Seyama, T.Suzuki
    • Journal Title

      J.Neurochem. 97

      Pages: 1369-1378

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] R-Opioid receptor internalization-dependent and -independent mechanisms of the development of tolerance to wopioid receptor agonists: comparison between etorphine and morphine.2006

    • Author(s)
      M.Narita, M.Suzuki, M.Narita, K.Niikura, A.Nakamura, M.Miyatake, Y.Yajima, T.Suzuki
    • Journal Title

      Neuroscience 138

      Pages: 609-619

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of tropioid receptor function in neurogenesis and neuroprotection.2006

    • Author(s)
      M.Narita, N.Kuzumaki, M.Miyatake, F.Sato, H.Wachi, Y.Seyama, T.Suzuki
    • Journal Title

      J.Neurochem. 97

      Pages: 1494-1505

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 薬物依存形成の分子機構 : 細胞間相互作用とダリア細胞の役割.2006

    • Author(s)
      成田 年, 宮竹真由美, 鈴木雅美, 葛巻直子, 鈴木 勉
    • Journal Title

      日本神経精神薬理学雑誌 26

      Pages: 33-39

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Direct evidence of astrocytic modulation in the development of rewarding effects induced by drug abuse.2006

    • Author(s)
      Narita M, Miyatake M, Narita M, Shibasaki M, Shindo K, Nakamura A, Kuzumaki N, Nagumo Y, Suzuki T
    • Journal Title

      Neuropsychopharmacology 31

      Pages: 2476-2488

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of neuronal NR2B subunit containing NMDA receptor-mediated Ca^2+ influx and astrocytic activation in cultured mouse cortical neurons and astrocytes.2006

    • Author(s)
      Kato H, Narita M, Miyatake M, Yajima Y, Suzuki T
    • Journal Title

      Synapse 59

      Pages: 10-17

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of gap junction in the expression of morphine-induced antinociception.2006

    • Author(s)
      Suzuki M, Narita M, Nakamuta A, Suzuki T
    • Journal Title

      Eur.J.Pharmacol. 535

      Pages: 169-171

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical δ-opioid receptor dysfunction.2006

    • Author(s)
      Narita M, Kuzumaki N, Narita M, Kaneko C, Hareyama N, Miyatake M, Shindo K, Miyoshi K, Nakajima M, Nagumo Y, Sato F, Wachi H, Seyama Y, Suzuki T
    • Journal Title

      J.Neurochem. 97

      Pages: 1369-1378

    • Related Report
      2006 Annual Research Report
  • [Journal Article] μ-Opioid receptor internalization-dependent and-independent mechanisms of the development of tolerance to μ-opioid receptor agonists : comparison between etorphine and morphine.2006

    • Author(s)
      Narita M, Suzuki M, Narita M, Niikuta K, Nakamura A, Miyatake M, Yajima Y, Suzuki T
    • Journal Title

      Neuroscience 138

      Pages: 609-619

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of δ-opioid receptor function in neurogenesis and neuroprotection.2006

    • Author(s)
      Narita M, Kuzumaki N, Miyatake M, Sato F, Wachi H, Seyama Y, Suzuki T
    • Journal Title

      J.Neurochem. 97

      Pages: 1494-1505

    • Related Report
      2006 Annual Research Report
  • [Journal Article] モルヒネ依存における持続的神経内プロテインキナーゼCの活性化と細胞・細胞間相互作用。2006

    • Author(s)
      成田 年, 宮竹真由美, 鈴木雅美, 鈴木 勉
    • Journal Title

      日本薬理学雑誌 127

      Pages: 32-35

    • NAID

      10017495082

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 薬物依存形成の分子機構 : 細胞間相互作用とグリア細胞の役割。2006

    • Author(s)
      成田 年, 宮竹真由美, 鈴木雅美, 葛巻直子, 鈴木 勉
    • Journal Title

      日本神経神薬理学雑誌 26

      Pages: 33-39

    • NAID

      10017328033

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Long-lasting change in brain dynamics induced by methamphetamine : enhancement of protein kinase C-dependent astrocytic response and behavioral sensitization.2005

    • Author(s)
      M.Narita, M.Miyatake, M.Shibasaki, M.Tsuda, S.Koizumi, M.Narita, Y.Yajima, K.Inoue, T.Suzuki
    • Journal Title

      J. Neurochem. 93

      Pages: 1383-1392

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Implication of cyclin-dependent kinase 5 in the development of psychological dependence on and behavioral sensitization to morphine.2005

    • Author(s)
      M.Narita, M.Shibasaki, Y.Nagumo, M.Narita, Y.Yajima, T.Suzuki
    • Journal Title

      J. Neurochem. 93

      Pages: 1463-1468

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of spinal metabotropic glutamate receptor 5 in the development of tolerance to morphine-induced antinociception.2005

    • Author(s)
      M.Narita, M.Suzuki, M.Narita, K.Niikura, A.Nakamura, M.Miyatake, T.Aoki, Y.Yajima, T.Suzuki
    • Journal Title

      J. Neurochem. 94

      Pages: 1297-1305

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glutamatergic neurotransmission and protein kinase C play a role in neuron-glia communication during the development of methamphetamine-induced psychological dependence.2005

    • Author(s)
      M.Miyatake, M.Narita, M.Shibasaki, A.Nakamura, T.Suzuki
    • Journal Title

      Eur. J. Neurosci. 22

      Pages: 1476-1488

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 薬物依存時におけるシナプス可塑性とグリア細胞.グリアから依存を考える.2005

    • Author(s)
      成田 年, 宮竹真由美, 鈴木雅美, 鈴木 勉
    • Journal Title

      日薬理誌 126

      Pages: 43-48

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 痛みとモルヒネ精神依存-基礎的知見に基づいたオピオイド使用のすすめ.2005

    • Author(s)
      成田 年, 南雲康行, 鈴木 勉
    • Journal Title

      治療学 39

      Pages: 788-792

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Long-lasting change in brain dynamics induced by methamphetamine : enhancement of protein kinase C-dependent astrocytic response and behavioral sensitization.2005

    • Author(s)
      M.Narita, M.Miyatake, M.Shibasaki, M.Tsuda, S.Koizumi, M.Narita, Y.Yajima, K.Inoue, T.Suzuki
    • Journal Title

      J.Neurochem. 93

      Pages: 1383-1392

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Implication of cyclin-dependent kinase 5 in the development of psychological dependence on and behavioral sensitization to morphine.2005

    • Author(s)
      M.Narita, M.Shibasaki, Y.Nagumo, M.Narita, Y.Yajima, T.Suzuki
    • Journal Title

      J.Neurochem. 93

      Pages: 1463-1468

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of spinal metabotropic glutamate receptor 5 in the development of tolerance to morphine-induced antinocicention.2005

    • Author(s)
      M.Narita, M.Suzuki, M.Narita, K.Niikura, A.Nakamura, M.Miyatake, T.Aoki, Y.Yajima, T.Suzuki
    • Journal Title

      J.Neurochem. 94

      Pages: 1297-1305

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glutamatergic neurotransmission and protein kinase C play a role in neuron-glia communication during the development of methamphetamine-induced psychological dependence.2005

    • Author(s)
      M.Miyatake, M.Narita, M.Shibasaki, A.Nakamura, T.Suzuki
    • Journal Title

      Eur.J.Neurosci. 22

      Pages: 1476-1488

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 薬物依存時におけるシナプス可塑性とダリア細胞.ダリアから依存を考える.2005

    • Author(s)
      成田 年, 宮竹真由美, 鈴木雅美, 鈴木 勉
    • Journal Title

      日薬理誌 126

      Pages: 43-48

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Long-lasting change in brain dynamics induced by methamphetamine : enhancement of protein kinase C-dependent astrocytic response and behavioral sensitization.2005

    • Author(s)
      M Narita, M Miyatake, M Shibasaki, M Tsuda, S Koizumi, M Narita, Y Yajima, K Inoue, T Suzuki
    • Journal Title

      J.Neurochem. 93

      Pages: 1383-1392

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Glutamatergic neurotransmission and protein kinase C : a role in neuro-glia communication during the development of methamphetamine-induced psychological dependence.2005

    • Author(s)
      M Miyatake, M Narita, M Shibasaki, A Nakamura, T Suzuki
    • Journal Title

      Eur.J.Neurosci. 22

      Pages: 1476-1488

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of spinal metabotropic glutamate receptor 5 in the development of tolerance to morphine-induced antinociception.2005

    • Author(s)
      M Narita, M Suzuki, M Narita, K Niikura, A Nakamura, M Miyatake, T Aoki, Y Yajima, T Suzuki
    • Journal Title

      J.Neurochem. 94

      Pages: 1297-1305

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Treatment for psychological dependence on morphine : Usefulness of inhibiting NMDA receptor and its associated protein kinase in the nucleus accumbens.2005

    • Author(s)
      M Narita, H Kato, K Miyoshi, T Aoki, Y Yajima, T Suzuki
    • Journal Title

      Life Sci. 77

      Pages: 2207-2220

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 薬物依存時におけるシナプス可塑性とグリア細胞.グリアから依存を考える2005

    • Author(s)
      成田 年, 宮竹真由美, 鈴木雅美, 鈴木 勉
    • Journal Title

      日本薬理学雑誌 126

      Pages: 43-48

    • Related Report
      2005 Annual Research Report

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

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