1996 Fiscal Year Final Research Report Summary
Molecular pharmacological study on he roles of brain cytokines in narcotic dependence
| Project/Area Number |
07457538
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
SATOH Masamichi Kyoto University, Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (80025709)
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| Co-Investigator(Kenkyū-buntansha) |
MINAMI Masabumi Kyoto University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (20243040)
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| Project Period (FY) |
1995 – 1996
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| Keywords | morphine / narcotics / dependence / cytokines / interleukins / microglia / neuro-immune interaction |
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| Research Abstract |
Intracisternal injection of interleukin-1beta was shown to suppress naloxone-precipitated with-drawal syndrome in morphine dependent mouse. This effect of interleukin-1beta was mediated by CRF and prostaglandin E2. In order to clarify the target cells for interleukin-1beta in the brain, we visualized the cells expressing type 1 and type 2 interleukin-1 receptors using an in situ hybridization technique. In morphine-dependent mouse, prostaglandin E2 suppressed the withdrawal syndrome through EP3 receptors. Prostaglandin EP3 agonists suppressed the withdrawal syndrome also in the morphine-dependent rats, and attenuated the experssion of c-fos mRNA in various brain regions including the locus ceruleus. Double in situ hybridization study revealed that most of the tyrosine hydroxylase mRNA-positive neurons in the locus ceruleus expressed mu-opioid receptor mRNA and more than half of those neurons were positive to EP3 receptor mRNA,indicating that an EP3 agonist acts on the locus ceruleus noradrenergic neurons expressing mu-opioid receptors. EP3 agonists possibly suppress the excitation of the locus ceruleus noradrenergic neurons to inhibit the morphine withdrawal syndrome precipitated by naloxone.
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