Abstract
In mammals, circadian rhythms are driven by a pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Isolated SCN cells show clear circadian rhythm of arginine vasopressin (AVP) release in cell or slice culture. This system is suitable to examine the effect of drugs including neurotransmitters and metabolic inhibitors. Using this system we examined the effect of tetrodotoxin (TTX) on the circadian rhythm. While TTX is known to reduce the expression of per1 and per2 mRNA, the previous reports have shown that the application of TTX has no effect on the phase of the rhythm either in vivo or in vitro. When TTX was applied to the culture, AVP release was markedly reduced. TTX also induced phase shift in a time-dependent manner. A four-hour application of TTX started in mid to late subjective day induced phase advance and that started in late subjective night to early subjective day induced phase delay. The phase response curve was very similar to that induced by dark pulse or non-photic stimuli. The data indicate that deprivation of neuronal firing changes the circadian rhythm. [Jpn J Physiol 55 Suppl:S198 (2005)]
