Behavioral study on mergocriptine (CBM36-733) by ambulatory activity in mice: repeated administration and interaction with methamphetamine.
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.
Kuribara
H
H
Division for Behavior Analysis, Gunma University School of Medicine, Maebashi, Japan.
Asami
T
T
Saito
T
T
Ida
I
I
Tadokoro
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004347:Drug Interactions; D004873:Ergolines / Q000737:chemistry / Q000494:pharmacology*; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013997:Time Factors
D003692:Delayed-Action Preparations; D004873:Ergolines; D008694:Methamphetamine; C067380:mergocriptine