[Characteristics of reverse tolerance to ambulation-increasing effect of methylphenidate after repeated administration in mice].
Effects of repeated administration of methylphenidate (MPD) 2, 4, 8 and 16 mg/kg, sc on ambulatory activity in adult male mice of old strain were studied. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 90-150 min after the drug administration. The repeated administration of MPD 2 and 4 mg/kg at intervals of 3-4 days, and 4 mg/kg at intervals of 7 days produced an augmentation in the sensitivity of the mice, i.e., a reverse tolerance, to the ambulation-increasing effect of the drug. However, the repeated administration of MPD 4 mg/kg at intervals of 1 day, and 8 and 16 mg/kg at intervals of 3-4 days did not produce the reverse tolerance to it. The mice repeatedly given 16 mg/kg at intervals of 3-4 days exhibited an augmentation in stereotyped behaviors. The reverse tolerance, once produced, was well maintained 45 days after cessation of the repeated administration. Only a little reverse tolerance to MPD was produced in the mice repeatedly given the drug in their home cage, in which the mice were group-housed, and the extent was significantly less than that observed in the mice given the drug in the activity cage. In addition, the mice showing the reverse tolerance to MPD demonstrated an increase in sensitivity to methamphetamine as compared with the saline-given control mice. The present results suggest that the characteristics of reverse tolerance to the ambulation-increasing effect of MPD is almost identical with that after methamphetamine.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004361:Drug Tolerance; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*
D008774:Methylphenidate; D008694:Methamphetamine; D000661:Amphetamine