[EEG studies on the analeptic effect of montirelin hydrate (NS-3), a TRH analog, in posterior hypothalamic area-lesioned rats].
Effects of a novel TRH analog, montirelin hydrate (NS-3), on the EEG were compared with those of TRH in intact and posterior hypothalamic area (PHA)-lesioned rats. In the intact rats, NS-3 at 0.01 mg/kg and TRH at 1 mg/kg produced no changes in the sleep-waking cycle. NS-3 at 0.1 mg/kg caused an increase in the time spent in the arousal stage and delayed the onset of the slow wave sleep (SS). On the other hand, TRH at 10 mg/kg increased the time spent in the SS stage and decreased the time in the A1 stage during 2 to 4 hr after injection without increasing the arousal stage, although it delayed the onset of SS. No abnormal EEG was observed after NS-3 or TRH administration in the intact rats. Electrolytic ablation of the PHA elicited continuous behavioral resting and caused increases in the slow-wave components in the cortical EEG and loss of generation of the hippocampal rhythmic slow activity. NS-3 at 0.01 mg/kg and TRH at 1 mg/kg caused the reappearance of the hippocampal rhythmic slow activity. In addition, NS-3 at 0.1 mg/kg and TRH at 10 mg/kg decreased the slow-wave components and increased the fast-wave components in the cortical EEG. In conclusion, NS-3 showed a distinct analeptic effect with a 100-fold higher potency than that of TRH in both the intact and PHA-lesioned rats.
Mushiroi
T
T
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Shibahara
R
R
Ukai
Y
Y
Yoshikuni
Y
Y
Kimura
K
K
D000818:Animals; D001143:Arousal; D000697:Central Nervous System Stimulants; D004569:Electroencephalography / Q000187:drug effects*; D007034:Hypothalamus, Posterior / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D012890:Sleep; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; C031926:montirelin; D013973:Thyrotropin-Releasing Hormone