Effects of ethanol, caffeine and nicotine, pleasurable substances, on wheel-running and drinking in mice that were housed under a 12 : 12-hr light-dark schedule (lighting period ; 6 : 00-18 : 00) were investigated. All drug administrations were carried out at 11: 00, a mid-light period. Although ethanol (0.8-2.4 g/kg p.o.) scarcely changed both the wheel-running and drinking during the light period, it was followed by a strong suppression of both behaviors during the coming dark period (18 : 00-6 : 00). The same treatment with caffeine (1-10 mg/kg s.c.) produced significant increase in the drinking during the light period, but suppression of the wheel-running during the dark period. Nicotine (0.1-1 mg/kg s.c.) significantly suppressed the wheel-running, but not drinking, during the dark period. The coadministration of nicotine (0.1-1 mg/kg) with ethanol (2.4 g/kg) reduced the behavioral suppression during the dark period. Whereas nicotine (0.1-1 mg/kg) reduced the increased drinking during light period by caffeine (10 mg/kg), but enhanced the caffeine-induced behavioral suppression during the dark period. These results indicate that the administration of pleasurable substances in the mid-light period results in a delayed effect which is characterized by a suppression of either and/or both wheel-running and drinking during the coming dark period starting 7 hr after the administration, and that nicotine acts to antagonize the effect of ethanol, but contrally to enhance the effect of caffeine.