Antidepressants and food restriction cycles: evidence for multiple pacemakers in rodents

Studies involving the suprachiasmatic nuclei (SCN) provide insufficient evidence to support the SCN as master pacemaker(s) in the rodent circadian system. Restricted feeding (RF) cycles act as strong zeitgebers for activity and corticosterone rhythms and provide support for the existence of important secondary pacemakers. These proposed pacemakers show anticipatory behavior, a limited range of entertainment for RF cycles, and prolonged free runs under certain circumstances. Additional evidence supporting a multiple pacemaker model of rodent circadian organization comes from studies involving antidepressants. Lithium treatment lengthens the free-running tau of rat activity rhythms and shifts the range of entrainment towards longer zeitgeber cycles. Lithium also phase delays many rodent rhythms but does not appear to affect the SCN-pineal axis. These data are difficult to explain without involving more than one pacemaker. Models of the rodent system can be developed incorporating multiple pacemakers. To test these models, a multivariate approach will be required. Combining the labeled 2-deoxyglucose method for metabolic mapping and the procedures of fractional desynchronization with antidepressant psychopharmacology and RF cycles may prove to be an important multivariate approach.