| 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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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
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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 / 口腔ジスキネジア / 顎運動パターン / 線条体腹外側部 / 黒質網様部 / 上丘外側深層部 / 脚内核 / 上丘 |
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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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