Electronic Thesis and Dissertation Repository


Doctor of Philosophy


Anatomy and Cell Biology


Dr. Michael Lehman


Studies suggest that the circadian timing system exerts an important influence on responses to rewarding stimuli. Diurnal rhythms in the rewarding value of amphetamine and mating behavior were observed, but differed in the pattern of their timing. Daily fluctuations in reward were correlated with oscillations in mesolimbic dopaminergic activity in both the nucleus accumbens (NAc) and ventral tegmental area (VTA), with a peak in NAc coinciding with the peak of sex reward, while the peak in the VTA associated with the peak in amphetamine reward. Also, rhythmic expression of the marker of neural activation, cFos, was observed in NAc, medial prefrontal cortex (mPFC), and VTA, with peak expression during the late night. Rhythmic clock protein expression was observed in the NAc, suggesting intrinsic circadian regulation of reward. However, absence of clock gene oscillations in the VTA suggests that rhythms in mesolimbic activity are also driven by a timing signal originating elsewhere; and the mPFC was hypothesized to be a key mediator. The effects of mPFC lesions or inactivation on diurnal rhythms in neural activation and amphetamine reward were determined. Lesions attenuated the peak in cFos-IR in the NAc, eliminating the diurnal rhythm, but had no effect on VTA rhythms. Moreover, daily differences in amphetamine reward were eliminated by mPFC lesions and inactivation, via an increase at the nadir. Together, these results indicate that diurnal rhythms of mesolimbic activity may be functionally relevant for rhythms in reward and that the mPFC plays a critical role in mediating such diurnal fluctuations.