Thus, our data clearly demonstrate that RF is a much stronger entraining cue for SHR than for Wistar rats; CHIR-99021 However, the underlying mechanism is not clear. Nevertheless, based on the published data, it is plausible to speculate that brain active mediators such as ghrelin and/or orexin may play a role in FAA. Their involvement in the mediation of FAA has previously been suggested because their deficiency resulted in decreased FAA in mice. CPI-613 Interestingly, ghrelin plasma levels as well as orexinergic activity in the brain were found to be elevated in SHR compared with controls. It remains to be tested whether these anomalies may contribute to the higher FAA response to RF in this rat strain. To test the hypothesis that the enhanced food anticipatory activity might result from a higher sensitivity of the circadian system to changes in feeding conditions, we determined the daily profiles of clock gene expression in the SCN and peripheral clocks of SHR and Wistar rats. Our previous data demonstrated that under ad libitum feeding conditions, the circadian system of SHR exhibits distinct differences when compared with that of Wistar rats. Specifically, the SHR exhibited a positive phase angle of entrainment of the locomotor activity rhythms that was likely due to a phaseadvanced SCN clock. The current data demonstrate that the phasing of the clock gene expression profiles in the SCN of SHR is not affected by RF, a result which is in good agreement with our previous findings in Wistar rats as well as with findings in all other species studied so far. Therefore, the higher sensitivity of SHR to RF, as reflected by the stronger FAA and phase advances of the locomotor activity in SHR, was not mediated by the SCN. Nevertheless, the question remains whether the positive phase angle of entrainment under ad libitum conditions in SHR may contribute to the effect of RF on the phasing of their locomotor activity. RF has been widely recognized as a strong entraining signal to some peripheral clocks, including those in the liver and colon. Our previous data revealed that the phasing and amplitude of the circadian clock oscillation in the liver did not differ between SHR and Wistar rats under ad libitum conditions, whereas the clock in the colon was advanced and dampened. In the present study, RF significantly phase advanced the daily profiles of clock gene expression in both peripheral tissues according to the time of food presentation in both rat strains. The colonic clock responded to RF in a very similar manner in both rat strains. However, obvious strain-dependent differences in the response to RF were detected in the liver. Whereas RF suppressed the oscillation of clock gene expression in the liver of the Wistar rats, no such suppression was detected in the SHR. Furthermore, in the SHR the amplitude of the Per2 expression rhythm increased significantly in response to RF. These results demonstrate that the oscillation of the hepatic clock is facilitated in SHR exposed to RF. The most striking difference between the two rat strains was found in the effect of RF on the temporal control of the Bmal2 mRNA profiles. In the Wistar rats, the Bmal2 expression did not exhibit circadian variation under ad libitum conditions and became expressed rhythmically with a very low amplitude under RF. However, the low-amplitude Bmal2 oscillation was not in phase with Bmal1 under RF and instead remained in approximately the same phase as Bmal1 under the ad libitum feeding conditions. Therefore, it is uncertain whether RF indeed phase-shifted Bmal2 expression in the liver of the Wistar rats. In contrast, in the SHR, Bmal2 was expressed with a low amplitude under ad libitum conditions, and the amplitude of the rhythm increased and was significantly phase advanced under RF. Importantly, in the SHR, both Bmal paralogs were in the same phase under RF.