ENHANCED STIMULANT EFFECTS OF d-AMPHETAMINE IN RATS TREATED CHRONICALLY 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 treated for 14 days with saline or reserpine. Amphetamine caused greater stimulation of motor activity in animals treated chronically with reserpine. A greater stimulation was also observed after a single dose of reserpine, as previously reported. d-Amphetamine, 0.5 to 1 mg/kg, administered to the chronic reserpine-treated rats, caused significantly higher activity than similar doses given to chronic saline-treated rats. Data for the chronic reserpine- and chronic saline-pretreatment groups were compared to data previously reported for rats treated acutely with saline or reserpine. Both reserpine treatments produced similar alterations in the d-amphetamine dose-response curves when compared to curves obtained from either saline-treated group. These changes were characterized by an increase in the slope of the dose-response curves, significant increases in both the peak drug effects and cumulative drug effects and increased durations of amphetamine-induced stimulation (only for rats treated chronically with reserpine). Chronic reserpine-treated rats were significantly more sensitive than acute reserpine-treated animals to the stimulant action of d-amphetamine. In addition, the chronic reserpine-treated group showed a marked sensitivity to the toxic effects of amphetamine. These data support the proposal by Dahlström and his coworkers that chronic reserpine pretreatment results in a supersensitivity of the "denervation" type in central adrenergic neurons.