Altered expression of circadian clock gene, mPer1, in mouse brain and kidney under morphine dependence and withdrawal

Abstract

Every physiological function in the human body exhibits some form of circadian rhythmicity. Under pathological conditions, however, circadian rhythmicity may be dusrupted. Patients infected with HIV or addicted to drugs of abuse often suffer from sleep disorders and altered circadian rhythms. Early studies in Drosophila suggested that drug seeking behavior might be related to the expression of certain circadian clock genes. Our previous research showed that conditioned place preference with morphine treatment was altered in mice lacking the Period-1 (mPer1) circadian clock gene. Thus, we sought to investigate whether morphine treatment could alter the expression of mPer1, especially in brain regions outside the SCN and in peripheral tissues. Our results using Western blot analysis showed that the mPER1 immunoreactivity exhibited a strong circadian rhythm in the brains of the control (Con), morphine-dependent (MD), and morphine-withdrawal (MW) mice. However, the phase of the circadian rhythm of mPER1 expression in the brains of MD mice significantly differed from that of the Con mice (p < 0.05). In contrast to mPER1 expression in the brain, the circadian rhythm of mPER1 immunoreactivity in the kidneys was abolished after morphine administration, whereas the Con mice maintained robust circadian rhythmicity of mPER1 in the kidney. Therefore, the effect of morphine on the circadian clock gene mPer1 may vary among different organs, resulting in desynchronization of circadian function between the SCN and peripheral organs. Originally published Journal of Circadian Rhythms, Vol. 4, No. 9, Aug 2006.