1994 Fiscal Year Final Research Report Summary
Effects of general anaesthetics and sedatives on central dopaminergic neuronal activity : a microdialysis study
| Project/Area Number |
04671138
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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 |
Functional basic dentistry
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| Research Institution | Nihon University |
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Principal Investigator |
KOSHIKAWA Noriaki Nihon University, School of Dentistry, Associate Professor, 歯学部, 助教授 (80130491)
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| Co-Investigator(Kenkyū-buntansha) |
TAKADA Koji Nihon University, School of Dentistry, Lecturer, 歯学部, 講師 (00216657)
KANAYAMA Toshiyoshi Nihon University, School of Dentistry, Professor, 歯学部, 教授 (40224589)
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| Project Period (FY) |
1992 – 1994
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| Keywords | Striatum / Nucleus accumbens / Dopamine release / Benzodiazepine receptor / Adenosine receptor / alpha_2-Adrenoceptor / Opioid receptor / Microdialysis |
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| Research Abstract |
Effects of benzodiazepine anaesthetics or sedatives on central dopaminergic neuronal activity were studied by using in vivo brain microdialysis to measure dopamine release from the striatum and the nucleus accumbens. Effects of the drugs often coadministered in clinic with the anaesthetics, i.e.clonidine and fentanyl, on central dopaminergic neuronal activity were also studied. Intravenous injections of midazolam and flunitrazepam decreased striatal dopamine release in a dose-dependent manner. Flumazenil also did not affect striatal dopamine release, but it prevented the effects of midazolam and flunitrazepam. Flunitrazepam also decreased striatal dopamine release when infused into the striatum, but it failed to affect the dopamine release when infused into the ipsilateral substantia nigra. Central administrations of midazolam were effective only when the drug was infused into both sites simultaneously. Intravenous injections of midazolam also dose-dependently decreased dopamine release from the nucleus accumbens. In contrast, the benzodiazepine receptor inverse agonist, beta-CCE,dosedependently increased the dopamini release. The effects of both drugs were prevented again by flumazenil. Moreover, adenosine receptors were not suggested to be involved in the benzodiazepine receptor-mediated dopamine decrease from the nucleus accumbens. Clonidine, an alpha_2-adrenoceptor agonist, decreased dopamine release from the nucleus accumbens, and enhanced the effects of midazolam. The results are suggestive of clinical use of clonidine to reduce the anaesthtic requirement of midazolam when used as a premedicant. Fentanyl, an opioid analgesic, increased dopamine release from the nucleus accumbens in a does-dependent manner. The effects were suggested to be mediated by the nucleus accumbens mechanisms. Furthermore, the effects of fentanyl was inhibited by midazolam infused into the nucleus accumbens but not infused into the ventral tegmental area.
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