Metabolic abnormalities caused by 3-acetylpyridine in the cerebral motor regions of rats: partial recovery by thyrotropin-releasing hormone.

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 (75 mg/kg, i.p.) on local cerebral glucose utilization (LCGU) in various brain regions. The effects of anti-ataxic agents, thyrotropin-releasing hormone (TRH) (10 mg/kg, i.p.) and its mimetic agent taltirelin hydrate (1 mg/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.