Sensitization to locomotor effects of methylphenidate in the rat.

A computerized activity monitoring system was used to investigate whether repeated exposure to methylphenidate (MPD) could produce sensitization to its locomotor effects in the rat. Male Sprague-Dawley rats were housed in test cages and activity was recorded continuously for 16 days as follows: Baseline activity (Day 1-2), recording following saline injection (Day 3), MPD Challenge Doses--either 0.6, 2.5, or 10 mg/kg of MPD (Day 4); five days of a repeated dose of 2.5 mg/kg (Day 5-9), five additional recording days of no treatment (Days 10-14), and MPD Re-Challenge (Day 15). Each group was re-challenged with the same doses as on day 4. Recording was resumed for an additional post-treatment day (Day 16). All injections were at 14:00. Horizontal activity, total distance, vertical activity, stereotypic activity, and number of stereotypic movements were recorded and analyzed. An augmented response (i.e., sensitization) was observed only to the lower MPD doses of 0.6 and 2.5 mg/kg. The sensitized response was more pronounced for forward ambulation than for rearing, with a complete lack of sensitization to the stereotypic effects of MPD.