[Effects of mosapramine (Y-516), a new dopamine D2 antagonist, on reverse tolerance after repeated administration of methamphetamine by means of the ambulation-increasing effect in mice].
Effects of mosapramine (Y-516), a new dopamine D2 antagonist, on reverse tolerance (sensitization) after repeated administration of methamphetamine (MAP; 2 mg/kg, s.c.) were investigated by means of ambulatory activity in mice; and they were compared with those of clocapramine (CCP), bromperidol (BPD) and chlorpromazine (CPZ). Y-516 (0.3, 1, 3 and 10 mg/kg, p.o.), CCP (3, 10 and 30 mg/kg, p.o.), BPD (0.1, 0.3 and 1 mg/kg, p.o.), CPZ (1, 3 and 10 mg/kg, p.o.) or 0.5% methylcellulose (MC; solvent, p.o.) were given to mice 30 min before MAP administration. The ambulatory activity was measured by tilting-type activity changes for 3 hr after MAP. These treatments were repeated 5 times at 3-4 day intervals. Then MAP alone was challenge-administered to all of these mice 3-4 days after the final administration. Marked reverse tolerance was produced after repeated administration of MC plus MAP. On the other hand, the ambulation-increasing effect of MAP was suppressed dose-dependently in groups pretreated with Y-516 or comparison-drugs, although the development of reverse tolerance was not completely inhibited after the repeated administration. In the challenge-administration of MAP, the ambulation-increasing effect was dose-dependently suppressed in the Y-516 group or the comparison-drug plus MAP group as compared with that in the MC plus MAP group.
Uchihashi
Y
Y
Division of Behavior Analysis, Gunma University School of Medicine, Maebashi, Japan.
Morimoto
T
T
Tadokoro
S
S
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists; D004361:Drug Tolerance; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006220:Haloperidol / Q000031:analogs & derivatives / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D014149:Tranquilizing Agents / Q000494:pharmacology*
D001552:Benzazepines; D003984:Dibenzazepines; D018492:Dopamine Antagonists; D004365:Drugs, Chinese Herbal; D014149:Tranquilizing Agents; C076165:gosha-jinki-gan-ryo extract; C054591:hachimijiogan; C046384:mosapramine; D008694:Methamphetamine; C000449:3-chlorocarpipramine; D006220:Haloperidol; C006820:bromperidol; D002746:Chlorpromazine