| Co-Investigator(Kenkyū-buntansha) |
TOMIYAMA Katsunori Nihon University, School of Dentistry, Associate Professor, 歯学部, 助教授 (40197942)
SAIGUSA Tadashi Nihon University, School of Dentistry, Assistant Professor, 歯学部, 講師 (50277456)
IKEDA Hiroko Nihon University, School of Dentistry, Research Assistant, 歯学部, 助手 (70297844)
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| Research Abstract |
The mechanisms underlying the development of drug-induced oral dyskinesia were studied by examining functions of the basal ganglia, particularly with respect to receptor-receptor interactions within the nucleus. In the studies using rat jaw moving model, evidence was provided for the regulatory role of striatal angiotensin AT_1 receptors in the ventrolateral striatum in dopamine D_1/D_2 receptor-mediated stereotyped jaw movements. It was also provided that GABA_A receptors in the output stations from the basal ganglia, such as the superior colliculus, retrorubral field and ventral pallidum, play an important role in the production of D_1/D_2 receptor-mediated repetitive jaw movements. In addition, reduction in the functions of postsynaptic D_1/D_2 receptors and acetylcholine receptors in the ventrolateral striatum was found in spontaneously hypertensive rats. In jaw movement studies using mutant mice with congenic dopamine receptor subtypes knockout, it was found that D_2 receptors exert differential regulation of individual orofacial movement topographies in a manner that is distinct form, and sometimes opposite to, that of their D_<1A> counterparts. Conversely, D_3,D_4 and D_5 receptors exert only miner regulation of such movements.
In the studies using rat turning model, it was found that opioid, AMPA, NMDA and GABA_A receptors in the nucleus accumbens shell play an important role in the induction of shell-specific D_1/D_2 receptor-mediated turning behaviour. Moreover, the pedunculopontine tegmental nucleus was shown to play a role as a relay station in the display of the shell-specific D_1/D_2 receptor-mediated turning behaviour. In the studies using in vivo brain microdialysis, evidence for characteristic profiles of putative selective opioid receptor agonists, TAN-67,endomorphin-1 and endomorphn-2, on striatal dopamine release mechanisms was provided.
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