Changes in feeding and locomotion induced by amphetamine analogs in rats

Studies of the biobehavioral actions of psychostimulants commonly focus on locomotion and less commonly on feeding, and only rarely are these measures considered in conjunction within the same animal. The present study compared the impact of (+)-amphetamine and three amphetamine analogs, PAL-287, PAL-313, and PAL-353, on eating and locomotion assessed concurrently using an automated activity/feeding chamber during a daily 45 min session. Each analog is a potent releaser of norepinephrine and of dopamine, but exerts differential serotonin-releasing activity (PAL-287>PAL-313>amphetamine>PAL-353). Rats were tested with each of five doses of drug (0, 2, 4, 8, or 16 micromol/kg, i.p.), given in equimolar concentrations and in random dose order. PAL-353, an analog with minimal serotonin-releasing capacity, markedly stimulated forward locomotion at 2, 4, 8 and 16 micromol/kg, as did amphetamine, whereas PAL-287 and PAL-313 did not. In contrast to the locomotor findings, all four amphetamine-like drugs exerted similar effects on the suppression of food intake. These results suggest that the capacity of an amphetamine analog (i.e. amphetamine and PAL-353) to stimulate serotonin release can diminish its psychostimulant action on locomotion, but does not reliably augment drug-induced hypophagia.