Role of astrocytes in rewarding effects of drugs of abuse
| Project/Area Number |
17500264
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Hoshi University, School of Pharmacy and pharmaceutical Sciences |
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Principal Investigator |
NARITA Minoru Hoshi University, School of Pharmacy and pharmaceutical Sciences, Department of toxicology, Associate professor, 薬学部, 助教授 (40318613)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| 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)
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| Keywords | Glial 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 |
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| 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.
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Report
(3 results)
Research Products
(46 results)
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[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
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Journal Title
J. Neurochem. 97
Pages: 1369-1378
Description
「研究成果報告書概要(和文)」より
Related Report
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[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
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Journal Title
J.Neurochem. 97
Pages: 1369-1378
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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
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Journal Title
J.Neurochem. 97
Pages: 1369-1378
Related Report
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