Over the last 30 years, interest has been growing steadily in the functional role of the pineal gland and the action of its major hormone, melatonin (MEL). As a neuroendocrine transducer of photoperiodic and other environmental information, the pineal gland plays a significant role in the temporal organizational of many physiological and behavioral processes. Alterations in pineal function have been associated with several conditions of central nervous system (CNS) origin that affect humans, such as motor and sleep disorders and endogenous depression. Yet, much remains to be learned regarding MEL's actions in the brain. The overall objective of this proposal is to expand our knowledge of the influence of MEL on CNS processes. Specifically, we will test the hypothesis that the action of MEL in the brain is an important element in the control of brain arousal level. We propose to use the ground squirrel (Citellus lateralis) as a model system because of the wide range of naturally-occurring changes in brain arousal level that characterize the mammalian hibernator. Thus, MEL will be centrally administered at different doses into specific brain areas in the hibernation and non- hibernation states, and its effects on brain arousal level will be determined. In hibernating animals, the effects of MEL and the MEL receptor antagonist, luzindole, on the duration and depth of this depressed state will be determined using a computer-controlled monitor of hibernation status daily recordings of body temperature and heart rate. In the non-hibernating state, the effects of MEL and luzindole on the brain arousal level will be assessed electrophysiologically in order to measure the effects of MEL action on sleep latency and duration. Liquid chromatography with electrochemical detection will be used to explore cellular mechanisms of MEL's action. The information we gain from this study will further our understanding of the mechanisms involved in the control of arousal level in the brain and increase our general knowledge of MEL's actions in the mammalian brain. Student involvement will be actively encouraged in all aspects and at all levels of the project.
