JPET #99010 1 Modafinil and circadian rhythms in Syrian hamsters: Assessment of the chronobiotic potential of a novel alerting compound

In Syrian hamsters, behavioral procedures for inducing arousal (e.g., running in a novel wheel or gentle handling) can shift circadian rhythms when applied during the usual sleep period (‘subjective day’) and can attenuate phase shifts to light during the active period (‘subjective night’). This raises the possibility that drugs that affect behavioral state may have ‘chronobiotic’ potential. We characterized the effects of modafinil, an atypical alerting compound, on circadian rhythms in male Syrian hamsters. EEG recordings and video observations confirmed that modafinil dose-dependently increases wakefulness at the expense of slow-wave and paradoxical sleep with no increase in locomotor activity per unit time awake. Despite inducing arousal, modafinil at these doses (150 or 300 mg/kg), administered in the subjective day or early or late in the subjective night, did not perturb circadian phase. Modafinil (300 mg/kg) also had no effect on phase shifts to light exposure either early or late in the night and did not alter the size of phase shifts induced by running in a novel wheel for 3 h during the mid-day. Modafinil (300 mg/kg) did, however, decrease by ~50% the amount of novel wheelstimulated running, moving leftward the dose-response relation between wheel revolutions and shift magnitude. These results indicate that, in Syrian hamsters, modafinil alone has no significant chronobiotic efficacy. Nevertheless, this agent may increase the sensitivity of the circadian pacemaker to non-photic stimuli, and may thus have some potential as a tool for promoting clock resetting in combination with behavioral strategies. This article has not been copyedited and formatted. The final version may differ from this version. JPET Fast Forward. Published on February 3, 2006 as DOI: 10.1124/jpet.105.099010 at A PE T Jornals on O cber 2, 2017 jpet.asjournals.org D ow nladed from