ENHANCED STIMULANT EFFECTS OF d-AMPHETAMINE ON THE SPONTANEOUS LOCOMOTOR ACTIVITY OF RATS TREATED WITH RESERPINE

¹ Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire

The effect of d-amphetamine in stimulating locomotor activity was measured in rats with and without reserpine pretreatment. As previously reported by Smith (1963, 1965) in mice, amphetamine caused greater stimulation of locomotor activity in animals that had received reserpine. However, dose-response curves in these rats are distinctly different from those derived from animals that did not receive reserpine. At all time periods of testing following the administration of reserpine (4, 13 and 25 hr) animals scored less than or the same as controls in their peak activity response to 0.25 to 1 mg/kg of amphetamine. On the other hand, a dose of 2.0 mg/kg of amphetamine induced a greater peak activity count in reserpine-pretreated rats than in controls. The latency to peak drug effect in reserpine-treated subjects, especially after the 4- and 13-hr pretreatments, was one-half that observed in the control rats. These results indicate that the reactivity of d-amphetamine in the brain is modified at all three time periods after the administration of reserpine. The duration of the stimulant action of d-amphetamine was markedly shortened in rats treated 4 or 13 hr before with reserpine. The cumulative drug-effect scores, the total number of locomotor activity counts above saline controls that were recorded from amphetamine-treated rats, were greater in reserpine-pretreated subjects only in the case of 2 mg/kg of amphetamine injected 25 hr after reserpine. These data suggest that the duration of stimulation and the cumulative drug effect after amphetamine are related to the size of the catecholamine store available for release from certain adrenergic sites in the brain. However, other factors appear to be implicated in the decreased latency and enhanced peak effect of d-amphetamine administered to reserpine-pretreated rats.

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