1993 Fiscal Year Final Research Report Summary
Changes of opiod receptors in brain obtained from morphine tolerant and dependent animals.
| Project/Area Number |
04670920
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | Gifu University |
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Principal Investigator |
OHTA Shuichiro Gifu University School of Medicine, Department of Anethesiology and Critical Care Medicine, Assistant Professor, 医学部・附属病院, 講師 (50144027)
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| Co-Investigator(Kenkyū-buntansha) |
NOZAKI Masakatsu Gifu University School of Medicine, Department of Anethesiology and Critical Car, 医学部, 助教授 (30021380)
SHIMONAKA Hiroyuki Gifu University School of Medicine, Department of Anethesiology and Critical Car, 医学部, 助教授 (90135202)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Opiod receptor / Receptor binding assay / Morphine tolerance / dependence / Alpha-2 adrenoceptor / Up regulation / oral controlled-release morphine / clonidine |
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| Research Abstract |
Morphine is well known to produce tolerance and dependence. The mechanisms for these phenomena are not clearly understood and there are a number of conflicting reports that chronic morphine administration decreases, increases, or leaves unchanged the number of opioid binding sites.
We examined the potency of MScontin^*(oral controlled-release preparation of morphine) to induce morphine dependence and also determined the change of mu, delta and kappa opioid receptor types in brain homogenates obtained from morphine-dependent guinea-pigs.
1. Guinea-pigs were implanted subcutaneously with MScontin^R(300mg/kg) and naloxone was employed to precipitate jumping behavior of withdrawal symptoms at various time. The highest degree of physical dependence was on the 2nd day after implantation. Therefore, the same period was chosen to investigate opipd receptor binding asssay.
2. Two days after implantation, the binding of^3H-DAGO(mu agonist), ^3H-DPDPE(delta agonist) and ^3H-U69593(kappa agonist) to
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brain membranes prepares from morphine dependent and control guinea-pigs was determined. Scatchard plot of the saturation binding data revealed a increase in Bmax values (maximum specific binding) and no change in the Kd values (equilibrium dissociation constants) of^3H-opiod ligand bindings obtained from morphine-dependent animals as compared to controls. These results indicate that brain mu, delta and kappa opiod receptors are up-regulated in morphine dependent guinea-pigs.
3. Similarly, we observed up-regulation of^3H-UK14304 (slective alpha-2 adrenergic agonist) binding sites in these morphine dependent animals.
4. THe contraction of the longitudinal muscle induced by electrical stimulation of the myenteric plexus-longitudinal muscle preparations obtained from morphine dependent animals were less depressed by morphine than the contractions evoked in preparations from control animals. Electorically evoked contractions of these preparations from morphine dependent animals showed reduced sencitivity to the depressant effocts of clonidine. So, cross-tolerance to clonidine was developed in the ileum isolated from morphine treated guinea-pigs. Less
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