Effect of amphetamine on the clock gene expression in rat striatum

Drug addicts have severe disruptions in many physiological and behavioral rhythms, such as the sleep/wake cycle. Interestingly, amphetamine, a psychostimulant, is able to alter many circadian patterns, which are independent of the master biological clock located in the suprachiasmatic nucleus. To increase our understanding of the circadian regulation of amphetamine on clock gene expression, rats received subcutaneous injections of d-amphetamine and the clock gene mRNA levels were analyzed using real-time PCR to obtain a daily profile. In the striatum, acute injection of d-amphetamine did not alter Period (Per)1, Per2 and Reverse erythroblastosis virus α (Rev-erbα) expressions. Chronic administration shifted the phase of Per1 and Per2 expressions from a nocturnal to diurnal pattern and advance shifted the peak of Rev-erbα in d-amphetamine-treated animals. In contrast, the rhythm of Brain and muscle Arnt-like protein-1 (Bmal1) was shifted from a diurnal to a nocturnal pattern by both acute and chronic treatments. These results demonstrated that chronic d-amphetamine treatment altered the expression of clock genes in the striatum. This might further influence the expression of related gene within the striatum and lead to behavioral and physiological changes which are associated to drug addiction.