EEG studies on the analeptic effect of montirelin hydrate (NS-3), a TRH analog, in posterior hypothalamic area-lesioned rats

Abstract

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.