Methylphenidate: diurnal effects on locomotor and stereotypic behavior in the rat

The dose-response relationship and time course of effect on motor activity after a single dose of methylphenidate given at different times of 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 injection of vehicle (saline) or of 0.6, 2.5, 10 or 40 mg/kg methylphenidate 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 horizontal activity, total distance, vertical activity, stereotypic activity, 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 duration of effect increased with dose. Ten mg/kg had the most robust effect 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 similar whether given during the light or dark phase, despite the large diurnal variations in baseline activity between the activity phases. The stereotypic effects of the highest dose of methylphenidate, however, varied between the light and dark phase, with a smaller stereotypic effect during the dark phase when compared to administration during the light phase.