1999 Fiscal Year Final Research Report Summary
Central mechanisms involved in the occurrence of oral dyskinesia
| Project/Area Number |
10671753
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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 |
Functional basic dentistry
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| Research Institution | Nihon University |
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Principal Investigator |
KOSHIKAWA Noriaki Nihon University School of Dentistry, Professor, 歯学部, 教授 (80130491)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Hiroko Nihon University School of Dentistry, Research Assistant, 歯学部, 助手 (70297844)
SAIGUSA Tadashi Nihon University School of Dentistry, Assistant Professor, 歯学部, 講師 (50277456)
TOMIYAMA Katsunori Nihon University School of Dentistry, Assistant Professor, 歯学部, 講師 (40197942)
HASEGAWA Megumi Nihon University School of Dentistry, Assistant, 歯学部, 副手 (90297846)
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| Project Period (FY) |
1998 – 1999
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| Keywords | jaw movements / animal model of oral dyskinesia / dopamine DィイD21ィエD2 / DィイD22ィエD2 receptor / acetylcholine receptor / GABAィイD2AィエD2 receptor / ventrolateral strialum / nucleus accumbens shell / descending pathway |
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| Research Abstract |
In rats treated chronically with antipsychotics, the display of spontaneous vacuous chewing is often considered as a valid animal model of tardive dyskinesia. Its face validity is underlined by the fact that both morphology and the onset of the oral movements elicited in rats bear a certain resemblance to that seen in man. However, its predictive validity by the fact that a long-term treatment with haloperidol, but not clozapine, increases vacuous chewing is not yet clear. This study revealed that both treatments similarly increased the behavious, showing that this paradigm was insufficient for predicting the drug-induced occurrence of oral dyskinesia in man. Changes in oral movements were objectively and reliably assessed with the help of the techinique, in which jaw movements are recorded by means of light-emitting diode attached to the mandible. Both apomorphine and a mixture of DィイD21ィエD2 and DィイD22ィエD2 receptor agonists increased jaw movements in haloperidol-treated but not clozapine-treated rats. The results show that the chosen pharmaco-behavioural assay is a new animal model of tardive dyskinesia that has predictive validity.
This study also examined the modulation of the different patterns of repetitive jaw movements, evoked by DィイD21ィエD2/DィイD22ィエD2 receptor or cholinoceptor stimulation in the ventrolateral striatum, by GABAィイD2AィエD2 receptors located in the dorsolateral part of the substantia nigra pars reticulata, entopeduncular nuckeus, ventral pallidum and superior colliculus. Moreover, this study examined the modulation of repetitive jaw movements, evoked by DィイD21ィエD2/DィイD22ィエD2 receptor stimulation in the nucleus accumbens shell, by GABAィイD2AィエD2 receptors located in the ventral pallidum and retrorubral field. The results demonstrate that GABAィイD2AィエD2 receptors in the brain sites examined can differentially modulate jaw movements elicited by dopaminergic and cholinergic stimulation.
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Research Products
(16 results)
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[Publications] Ikeda, H., Adachi, K., Hasegawa, M., Sato, M., Hirose, N., Koshikawa, N. and Cools, A.R.: "Effects of chronic haloperidol and clozapine on vacuous chewing and dopamine-mediated jaw movements in rats : evaluation of a revised animal model of tardive dyskinesia."J. Neural Transm. 106. 1205-1216 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Adachi, K., Ikeda, H., Hasegawa, M., Nakamura, S., Waddington, J.L. and Koshikawa, N.: "SK&F 83959 and non-cyclase-coupled dopamine DィイD21ィエD2-like receptora in jaw movements via dopamine DィイD21ィエD2-like/DィイD22ィエD2-like receptor synergism."Eur. J. Pharmacol. 367. 143-149 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Ikeda, H., Adachi, K., Hasegawa, M., Sato, M., Nakamura, S., Hirose, N., Koshikawa, N. and Waddington, J.L.: "SK&F 83959 an anomalous antagonist of dopamine-sensitive adenylyl cyclase, exhibits a dopamine DィイD21ィエD2-like receptor agonist profile in the regulation of jaw movements by DィイD21ィエD2-like : DィイD22ィエD2-like receptor synergism."Jpn. J. Pharmacol.. 79 Suppl. I. 44 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Adachi, K., Ikeda, H., Hasegawa, M., Sato, M., Nakamura, S., Gerstner, G.E. and Koshikawa, N.: "Role of GABAィイD2AィエD2 receptors in the superior colliculus in the production of rat repetitive jaw movements."Jpn. J. Pharmacol.. 79 Suppl. I.. 45 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Adachi, K., Ikeda, H., Hasegawa, M., Sato, M., Nakamura, S. and Koshikawa, N.: "Role of GABAィイD2AィエD2 receptors in the ventral pallidum and the retrorubral field in the rat accumbens-specific jaw movements."Jpn. J. Pharmacol.. 82 Suppl. I.. 73 (2000)
Description
「研究成果報告書概要(欧文)」より
