Anisomycin, an inhibitor of protein synthesis, perturbs the phase of a mammalian circadian pacemaker

Administration of the protein synthesis inhibitor, anisomycin, induced both advance and delay phase-shifts in the circadian rhythm of locomotor activity in hamsters maintained in constant darkness. The magnitude and direction of the phase shift was dependent on the circadian time of drug treatment. A second protein synthesis inhibitor, cycloheximide, also induced phase-shifts in the circadian rhythm of activity, while two drugs which mimic some of the side effects of protein synthesis inhibitors had no significant effect on the activity rhythm. The phase-response curve generated by anisomycin injections in the hamster is similar to the response curves that have been measured for protein synthesis inhibitors in micro-organisms and invertebrates. Thus, the biochemical mechanisms generating circadian oscillations in mammals may share common features with those found in very distantly related phylogenetic groups.