Effects of circadian cycle and time of testing on drug-induced anorexia in rats

Based on the results from a previous study conducted in our laboratory, the present experiment sought to replicate the finding that the magnitude of the anorexic effect of phenylpropanolamine (PPA) in rats is greater during the early dark phase than the early light phase of the circadian cycle. Moreover, the present study included two additional anorectic drugs, amphetamine and fenfluramine, as well as additional testing times in the middle of the respective phases of the circadian cycle. For the 1h feeding tests, all three anorectic drugs demonstrated a significant dose-dependent phase (Light/Dark) effect such that all three agents induced greater anorexia during the dark phase. The significance of the dark phase testing was also apparent after 4h of testing for PPA and amphetamine, but not for fenfluramine. Furthermore, during the 1h tests, PPA and amphetamine, but not fenfluramine, demonstrated significant test time interactions such that the greatest magnitude of anorexia was observed during the middle of the dark phase. The present data are intriguing in that the anorexic effects of these three drugs, which are believed to operate via three distinct neurochemical mechanisms, are modulated by the circadian cycle in a similar fashion during a 1 h feeding trial. Thus, the results of this study indicate that one salient factor (i.e. time of testing within the circadian cycle) may, in part, contribute to the variability often observed in feeding studies using different experimental protocols.