Dual regulation of clock gene Per2 expression in discrete brain areas by the circadian pacemaker and methamphetamine‐induced oscillator in rats

Jan 21, 2014The European journal of neuroscience

Clock gene Per2 expression in specific rat brain areas controlled by the body’s internal clock and methamphetamine-driven rhythms

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Abstract

Methamphetamine (MAP) treatment in rats induced behavioral rhythms independent of the circadian pacemaker, with relative coordination observed in SCN-intact rats.

The MAP-induced oscillator (MAO) was established by administering MAP in drinking water at a specific time for 14 days.
Behavioral rhythms in SCN-intact rats showed phase delays under ad libitum MAP conditions, indicating a level of coordination.
Circadian rhythms of the clock gene Per2 were slightly advanced in the olfactory bulb, caudate-putamen, and substantia nigra of R-MAP rats compared to controls.
In SCN-lesioned rats, MAO phase-shifted more slowly and lacked signs of coordination.
Significant phase shifts in Per2 rhythms were noted in the olfactory bulb and substantia nigra of SCN-lesioned rats compared to SCN-intact rats.
These results indicate that extra-SCN oscillators are involved in MAO and are influenced by both MAP and the SCN.

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Behavioral rhythms induced by methamphetamine (MAP) treatment in rats are independent of the circadian pacemaker in the suprachiasmatic nucleus (SCN). To know the site and mechanism of an underlying oscillation (MAP-induced oscillator; MAO), extra-SCN circadian rhythms in the discrete brain areas were examined in rats with and without the SCN. To fix the phase of MAO, MAP was supplied in drinking water at a restricted time of day for 14 days (R-MAP) and subsequently given ad libitum (ad-MAP). Plain water was given to the controls at the same restricted time (R-Water). Clock gene Per2 expression was measured by a bioluminescence reporter in cultured brain tissues. In SCN-intact rats, MAO was induced by R-MAP and behavioral rhythms were phase-delayed from the restricted time under ad-MAP with relative coordination. Circadian Per2 rhythms in R-MAP rats were not affected in the SCN but were slightly phase-advanced in the olfactory bulb (OB), caudate-putamen (CPU) and substantia nigra (SN) as compared with R-Water rats. Following SCN lesion, R-MAP-induced MAO phase-shifted more slowly and did not show a sign of relative coordination. In these rats, circadian Per2 rhythms were significantly phase-shifted in the OB and SN as compared with SCN-intact rats. These findings indicate that MAO was induced by MAP given at a restricted time of day in association with phase-shifts of the extra-SCN circadian oscillators in the brain dopaminergic areas. The findings also suggest that these extra-SCN oscillators are the components of MAO and receive dual regulation by MAO and the SCN circadian pacemaker.

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Dual regulation of clock gene Per2 expression in discrete brain areas by the circadian pacemaker and methamphetamine‐induced oscillator in rats

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