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.
Kinoshita
K
K
Pharmacology Department, Discovery Research Laboratory, Tanabe Seiyaku Co, Ltd, Toda, Saitama, Japan.
Watanabe
Y
Y
Asai
H
H
Matsuoka
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism; D008297:Male; D018716:Molecular Mimicry; D009498:Neurotoxins / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000819:agonists; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*
D009498:Neurotoxins; D011725:Pyridines; D018025:Receptors, Thyrotropin-Releasing Hormone; C010835:3-acetylpyridine; C065049:TA 0910; D013973:Thyrotropin-Releasing Hormone; D005947:Glucose