Enhanced stimulant properties of (+)-amphetamine after chronic reserpine treatment in the rat: mediation by hypophagia and weight loss

Rats were treated with daily i.p. injections of reserpine (0.5 mg/kg) or saline for 10 days. Twenty-four hours after the last injection they were given (+)-amphetamine (0.25, 0.50, or 1 mg/kg) or saline and their locomotor activity was measured for 3 hr. In accordance with previous reports, (+)-amphetamine induced a significantly greater stimulation of spontaneous activity after reserpine. The effect was variable however insofar as it was observed only in those animals that suffered marked weight loss during the reserpine treatment. In addition, when the heightened baseline activity of the groups chronically treated with reserpine was considered, the enhanced stimulant effects of (+)-amphetamine were no longer evident. In a second experiment, the food intake of the chronic saline animals was controlled so that both the reserpine and saline groups underwent similar weight losses during the 10-day injection procedure. In that experiment, chronic reserpine treatment failed on every measure to increase the stimulant effects of (+)-amphetamine. In contrast to the first experiment, on one measure (the lowest dosage which significantly increased activity) the saline pre-treated animals were more responsive to (+)-amphetamine than were the rats pretreated with reserpine. It is suggested that chronic reserpine administration continues to exert a mild sedative action which is completely masked and reversed by the marked increase in arousal which results from the reserpine-mediated hypophagia and weight loss. This starvation-induced arousal appears to interact with amphetamine-mediated locomotor stimulation to produce the increased responsiveness to amphetamine after chronic reserpine treatment.