Behavioral study on mergocriptine (CBM36-733) by ambulatory activity in mice: repeated administration and interaction...

Effects of repeated administration of mergocriptine (CBM36-733: CBM), a long-acting ergot derivative with an agonistic action on both dopamine D1 and D2 receptors, as well as interaction between CBM and methamphetamine (MAP: 2 mg/kg, s.c.), were investigated by ambulatory activity in mice. CBM at 4 mg/kg significantly suppressed the ambulatory activity, but significantly increased it at 16 mg/kg in the drug-naive mice. However, 4 and 8 mg/kg of CBM were effective for increasing the ambulatory activity when these doses were repeatedly administered for 9 times at intervals of 7 days. The same treatment with 16 mg/kg of CBM produced a reverse tolerance to the ambulation-increasing effect. The mice that had received CBM at 1 and 2 mg/kg, but not 4-16 mg/kg, demonstrated a significantly lower sensitivity to MAP than the saline-experienced mice. On the other hand, the repeated MAP administration induced not only a reverse tolerance to itself, but also a cross reverse tolerance to 8 and 16 mg/kg of CBM. Furthermore, the established reverse tolerance to MAP was scarcely attenuated by the repeated treatment with any doses of CBM, but rather enhanced by 8 and 16 mg/kg of CBM. The present results indicate that, although the dose-effect relations are partially different, the behavioral characteristics of CBM were almost identical with those of bromocriptine, another long-acting ergot derivative having antagonistic and agonistic actions on dopamine D1 and D2 receptors, respectively.