Abstract
Behavioral rhythms in mice were desynchronized from light-dark (LD) cycle under chronic methamphetamine(MAP) treatment. Our previous findings indicate that clock gene expression rhythms in the caudate-putamen(CPU) and parietal cortex(PC) are in phase with MAP-induced behavioral rhythms, whereas those in the SCN remains to entrain to LD cycle. These findings suggested that behavior rhythms in MAP treated animals were driven by an oscillator(s) outside the SCN. However, it is not known whether or not the CPU and PC are the site of oscillator. To identify the location of MAP-induced circadian oscillator, we examined Per1 expression rhythms in several regions of brain culture from mice under chronic MAP treatment. Transgenic mice expressing luciferase under the control of Per1 promoter (Per1-Luc) were treated with 0.005% MAP through drinking water until their spontaneous locomotor rhythms desynchronized from LD cycle. They were decapitated on the day when their activity onset reached to the light on phase, and the coronal brain slices of 300μm thick were cultured in the medium containing 0.1mM luciferin. Bioluminescence rhythms were continuously measured for 10 days. Comparing with un-treated control mice, MAP-treated mice exhibited significant phase differences in substantia nigra(SN). This result suggests that the MAP-induced circadian oscillation was generated in the SN. [J Physiol Sci. 2007;57 Suppl:S139]
