[Effects of repeated administration of bromocriptine on ambulatory activity in mice, and changes in methamphetamine...

Effects of repeated administration of bromocriptine, a long-acting dopamine agonist, as well as interaction between bromocriptine and methamphetamine were investigated by mean of ambulatory activity in mice. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 6 and 3 hr after administration of bromocriptine and methamphetamine, respectively. The repeated 5 times administration of bromocriptine and of methamphetamine was at intervals of 7 days and of 3-4 days, respectively. Bromocriptine tended to suppress the activity at low doses (1 and 2mg/kg, ip), but increased the activity at high doses (8 and 16 mg/kg, ip), showing biphasic effects depending on the doses administered. Both the ambulation-suppressing and -increasing effects of bromocriptine were enhanced when the drug was repeatedly administered. The mice that experienced the repeated administration of low doses and high doses of bromocriptine exhibited a decrease and an increase, respectively, in the sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg, sc). Repeated administration of methamphetamine (2 mg/kg, sc) elicited an increase in sensitivity not only to methamphetamine itself, showing reverse tolerance, but also to high doses of bromocriptine, showing cross reverse tolerance. However, the reverse tolerance to methamphetamine, once produced, was not affected by the repeated administration of low doses of bromocriptine.