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OBJECTIVE To explore role of the brain area as modulator and the underlying mechanism of the diurnal variation of cocaine reward.METHODS We examined the circadian rhythm of GSK-3β activity in SCN and reward-related brain areas in naive rats, day and night influence the acquisition of cocaine conditioned place preference (CPP) , cocaine CPP influence the GSK-3β activity in the brain areas described above, and the effect of GSK-3β inhibitor SB216763 microinjected bilateral VTA on cocaine CPP.