Changes in feeding and locomotion induced by amphetamine analogs in rats

Abstract

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.

Fig.1

Mean group changes in total distance traveled scores (cm) during successive 15 min periods for rats treated with either amphetamine (AMP) or with PAL-287, PAL-313, or PAL-353. Panel A: 0 umol/kg. Panel B: 2 umol/kg. Panel C: 4 umol/kg. Panel D: 8 umol/kg. Panel E: 16 umol/kg. The line above each symbol represents the SEM for that value.

Fig.2

Mean group cumulative food intake values during successive 15 min periods for rats treated with either amphetamine (AMP) or with PAL-287, PAL-313, or PAL-353. Panel A: 0 umol/kg. Panel B: 2 umol/kg. Panel C: 4 umol/kg. Panel D: 8 umol/kg. Panel E: 16 umol/kg. The line above each symbol represents the SEM for that value.

Fig.3

Panel A: Mean group changes in total distance traveled scores (cm) for rats injected with a random order dose series of 0, 2, 4, 8 or 16 umol/kg (i.p.) (+)-amphetamine (AMP), PAL-287, PAL-313, or PAL-353. The * symbol indicates a significant difference (P < 0.05) between the AMP group and either PAL-287 or PAL-313 groups at a particular dose, whereas the # symbol indicates a significant difference (P < 0.05) between the PAL-353 group and either PAL-287 or PAL-313 groups at a particular dose. Panel B. Mean group changes in food intake (0.1g) for rats injected with an random order dose series of 0, 2, 4, 8 or 16 umol/kg (i.p.) (+)-amphetamine (AMP), PAL-287, PAL-313, or PAL-353. The line above each symbol represents the SEM for that value.