Tolerance to amphetamine-induced impairment of rotarod performance in rats.

Acute administration of d-amphetamine sulfate (30 mg/kg, i.p.) caused muscle weakness and 80% failure in rotarod performance in rats. The incidence of performance failure progressively decreased to 30% in animals receiving d-amphetamine and tested daily for 8 days. A similar progressive reduction in performance impairment was observed in animals receiving d-amphetamine for 3, 5, or 7 days (12.5%) and evaluated only once after the last dose. The tolerance is attributable to a physiological or biochemical rather than learning phenomenon.