Modification by caffeine of the sensitization to methamphetamine and cocaine in terms of ambulation in mice.

The repeated administration of caffeine (CAF: 1, 3 and 10 mg/kg s.c.) alone 5 times at 3- to 4-day intervals did not produce any significant change in the sensitivity to the ambulation-increasing effects of CAF itself, methamphetamine (MAP: 1 and 2 mg/kg s.c.) and cocaine (COC: 10 and 20 mg/kg s.c.). Whereas, the repeated administration of MAP (1 and 2 mg/kg) and COC (10 and 20 mg/kg) produced sensitization to the individual drug effects. The combination of MAP or COC with CAF potentiated the effect, and sensitization was produced by the repeated 5-time administrations of the following combinations: MAP (1 mg/kg) with CAF (3 and 10 mg/kg), MAP (2 mg/kg) with CAF (1 and 3 mg/kg), COC (10 mg/kg) with CAF (1 mg/kg) and COC (20 mg/kg) with CAF (1 and 3 mg/kg). Moreover, the mice given COC (10 mg/kg) with CAF (3 and 10 mg/kg) and COC (20 mg/kg) with CAF (1 and 3 mg/kg) exhibited significantly higher sensitivity to challenge COC than those given COC alone. However, the sensitivities to challenge MAP of the mice given MAP with CAF were almost the same with those given MAP alone. These results suggest that, in terms of ambulation in mice, the combination of MAP or COC with CAF elicits potentiation of the acute stimulant effect, and that CAF is responsible in enhancement of COC sensitization, but not MAP sensitization.