Metabolic Abnormalities Caused by 3-Acetylpyridine in the Cerebral Motor Regions of Rats. Partial Recovery by Thyrotropin-Releasing Hormone.

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  • Kinoshita Kiyoshi
    Pharmacology Department,Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,Kawagishi 2-2-50,Toda,Saitama 335-8505,Japan
  • Watanabe Yumi
    Pharmacology Department,Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,Kawagishi 2-2-50,Toda,Saitama 335-8505,Japan
  • Asai Hidetoshi
    Pharmacology Department,Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,Kawagishi 2-2-50,Toda,Saitama 335-8505,Japan
  • Matsuoka Yuzo
    Pharmacology Department,Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,Kawagishi 2-2-50,Toda,Saitama 335-8505,Japan

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  • Metabilic Abnormalities Caused by 3-Acetylpyridine in the Cerebral Motor Regions of Rats:Partial Recovery by Thyrotropin-Releasing Hormone

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Abstract

Although 3-acetylpyridine(3-AP) induces several motor disturbances and it degenerates the olivocerebellar pathway, abnormalities caused by 3-AP in cerebral motor regions remain to be elucidated.Here we investigated the metabolic changes caused by 3-AP(75mg/kg, i.p.) on local cerebral glucose utilization(LCGU) in various brain regions.The effects of anti-ataxic agents, thyrotropin-releasing hormone(TRH)(10mg/kg, i.p.) and its mimetic agent taltirelin hydrate(1mg/kg, i.p.), on the 3-AP-induced change in LCGU were also investigated.The LCGU in the nuclei of the basal ganglia, thalamus, limbic structures and brainstem of 3-AP-treated rats was significantly lower than that of naive animals.However 3-AP increased the LCGU of the cerebellar nuclei.TRH restored depressed LCGU in the substantia nigra and ventral tegmental area.TRH tended to restore the lowered LCGU in several nuclei of 3-AP-treated rats.Moreover, taltirelin further increased the LCGU in the cerebellar nuclei.These results suggest that the motor disturbance of the 3-AP-treated rats may be due to not only degeneration of the olivocerebellar pathway but also dysfunction of the several areas that play a role in motor coordination.Moreover, the anti-ataxic action by TRH could result from metabolic restoration of the multiple motor-coordination-related areas.

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