Roles of central opioid, adenosine and peripheral adrenal systems in morphine-induced tolerance and dependence in rat
| Project/Area Number |
10672082
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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 |
Biological pharmacy
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| Research Institution | Fukuyama University |
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Principal Investigator |
SHIOMI Hirohito Faculty of Pharmacy and pharmaceutical Sciences, Fukuyama University, Professor, 薬学部, 教授 (60025715)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Yutaka Faculty of Pharmacy and pharmaceutical Sciences, Fukuyama University, Lecturer, 薬学部, 講師 (30217202)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | morphine tolerance / morphine dependence / adenosine / adenosine A1 receptor / adenosine A2 receptor / β-endorphin / N-acetyl-β-endorphin / 疼痛促通系 / アデノシンA2受容体 / マイクロダイアリシス / 疼痛制御系 / 頭痛促通系 |
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| Research Abstract |
In this studies we examined to determine the site of suppressive action of adenosine to morphine-tolerance by using intracerebral micro-injection technique. Centrally administered adenosine depressed morphine-induced analgesia via adenosine A1 receptor and theophylline and/or specific A1 receptor antagonists were able to suppressed the development of morphine-induced tolerance. In native rats, the micro-injections of morphine into the nucleus reticulates gigantocellularis (NRGC)/the nucleus reticularis paragigantocellularis (NRPG) and the periaqueductal gray matter (PAG), produced significant elevation of pain threshold. These effects were suppressed with simultaneous treatment of N6-cyclohexyladenosine (CHA), a specific A1 agonist. When micro-injected into the NRGC/NRPG and/or PAG, N-acetyl- β -endorphin(1-27)(NABE) also suppressed morphine-induced analgesia. The suppressive effects of CHA and NABE were reversed with simultaneous treatment of 8-cyclopentytheophylline (CPT), a specific A1 antagonist. In morphine-tolerant rats, a single micro-injection of morphine into the NRGC/NRPG and PAG, no longer produced an increase in pain threshold. However, analgesic effect of morphine were recovered with simultaneous treatment of morphine and CPT into the NRGC/NRPG and PAG. These results suggest that central adenosine system plays an important role in the formation of morphine-induced tolerance. On the other hand, in morphine-dependent rat, naloxone-induced abstinence signs were suppressed by intracerebroventricular (I. C. v.) injections of CHA and/or CGS21680, a specific A2 receptor agonist. Therefore, in the morphine-dependent condition, central adenosine may play a role in the suppression of morphine-withdrawal signs via A1 and A2 receptors.
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Report
(3 results)
Research Products
(4 results)
