RUI: Opioid Modulation of Circadian Rhythms

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The organization of animal behavior into twenty-four hour, or circadian, rhythmic cycles is a fundamental feature of the mammalian nervous system. There appear to be many physiological systems within mammals that are capable of generating their own twenty-four rhythms, although each is probably synchronized by one master time-keeping pacemaker within the brain. This master pacemaker is located in a group of cells organized into the suprachiasmatic nucleus, found just above the optic chiasm at the base of the mammalian brain. The suprachiasmatic nucleus receives input from multiple brain regions, but the major inputs come from the retina, intergeniculate nuclei of the thalamus, and the raphe nuclei in the brainstem. The timing of the circadian clock can be adjusted by input from each of these areas, analogous to moving the hands of the clock forward or backward in time. In this study, we will be focusing on input from the intergeniculate leaflet, input that adjusts the clock in response to behavioral stimuli independent of photic information arriving from the retina. In hamsters, intergeniculate input to the suprachiasmatic nucleus is mediated in part by endogenous enkephalin opioid systems and can be mimicked by administration of delta opioid drugs that activate the receptors for enkephalins (delta opioid receptors). Circadian rhythms in hamsters are modified by running in novel wheels, and also by the administration of benzodiazepines and serotonin-like drugs. Each of these stimuli involves the intergeniculate nuclei and thus may be mediated by delta opioid receptors. Therefore, this project will examine the connection between delta opioid receptors and the modification of circadian rhythms by running behavior and benzodiazepines. The results of this project will enhance our understanding of how the suprachiasmatic nuclei integrates information from various brain regions in determining how the time of the clock will be adjusted. This project will also significantly enhance the training of undergraduate students in the sciences, many of whom are planning a career as science teachers.