The dose-response relationship and time course of effect on motor acti
vity after a single dose of methylphenidate given at different times o
f the light/dark cycle was investigated using a computerized infrared
activity analysis system. After 5 to 7 days of acclimation and 2 days
of baseline activity recording, rats received a single subcutaneous in
jection of vehicle (saline) or of 0.6, 2.5, 10 or 40 mg/kg methylpheni
date at 08:00, 14:00, 20:00, or 02:00. Recording was then resumed for
an additional 36 to 48 hours. The locomotor indices analyzed were hori
zontal activity, total distance, vertical activity, stereotypic activi
ty, and number of stereotypic movements. Saline and 0.6 mg/kg did not
alter motor activity, but 2.5, 10 and 40 mg/kg significantly increased
(P < 0.01) motor activity. The time to the maximum effect and the dur
ation of effect increased with dose. Ten mg/kg had the most robust eff
ect on locomotor activity, while the largest dose, 40 mg/kg, elicited
a more focused stereotyped activity that limited the amount of forward
ambulation. A single injection of methylphenidate had only transient
effects. The locomotor stimulating effects of the lower doses were sim
ilar whether given during the Light or dark phase, despite the large d
iurnal variations in baseline activity between the activity phases. Th
e stereotypic effects of the highest dose of methylphenidate, however,
varied between the light and dark phase, with a smaller stereotypic e
ffect during the dark phase when compared to administration during the
light phase. (C) 1997 Elsevier Science B.V.