Anti-ataxic effects of TRH and its analogue, TA-0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area.
1. The mechanism of the anti-ataxic action of thyrotropin-releasing hormone (TRH) and its analogue. TA-0910, in the Rolling mouse Nagoya (RMN), an ataxic mutant mouse, has been investigated. 2. TRH (30 mg kg-1, i.p.) and TA-0910 (3 mg kg-1, i.p.) reduced the fall index (number of falls/spontaneous motor activity), an index of ataxia, 10-30 and 10-60 min after administration, respectively. 3. Relative local cerebral glucose utilization (LCGU) in the cerebellum and ventral tegmental area (VTA) of the rolling mouse was significantly smaller than that in normal animals. TRH (30 mg kg-1, i.p.) and TA-0910 (3 mg kg-1, i.p.) increased the relative LCGU value of the VTA but not of the cerebellum in rolling mice to the level of normal animals. 4. These results suggest that the ataxia of the rolling mouse may be due to dysfunction of the cerebellum and VTA, and that amelioration by TRH and TA-0910 could result from metabolic normalization of the VTA.
Kinoshita
K
K
Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd, Saitama, Japan.
Watanabe
Y
Y
Asai
H
H
Yamamura
M
M
Matsuoka
Y
Y
D000818:Animals; D001259:Ataxia / Q000188:drug therapy / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
C065049:TA 0910; D013973:Thyrotropin-Releasing Hormone; D005947:Glucose