CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY

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This grant proposal is a request for an ADAMHA RSDA (Level II). Humans and other animals display seasonal changes in body weight. The environmental signal for this response and for seasonal reproduction cycles in some species is daylength change, the neuroendocrine transducer of which is the pineal gland and its hormone, melatonin (MEL). Furthermore, the duration is the critical feature of the nocturnal MEL secretion profile. Siberian hamsters will be studied, a species that exhibit dramatic seasonal fluctuations in body fat following exposure to short 'winter-like' photoperiods. The goal of this research is to identify the CNS target sites of MEL that trigger seasonal changes in body fat. The target sites of MEL will be identified by determining: 1) the localization of MEL binding in brain using autoradiography and examining environmental and hormonal influences on MEL binding (e.g., time-of-day, photoperiod, pinealectomy [PINX]), 2) whether lesions of MEL binding sites will eliminate short day-induced changes in body weight and fat, food intake and reproductive status, 3) whether lesions of MEL binding sites block short day responses by eliminating the reception of the short day MEL signal by giving PINX hamsters bearing lesions programmed subcutaneous (s.c.) MEL infusions that mimic the MEL signal associated with transfer to short days, 4) the neural input and output pathways of the target sites using new, highly sensitive anterograde and retrograde tracers, 5) whether short day responses elicited by programmed s.c. MEL infusions can be blocked by selective damage of fibers of passage or cell bodies with microknife cuts and neurotoxins, respectively, in PINX hamsters, 6) whether short day responses can be elicited by directly microinfusing MEL into the target sites in PINX hamsters, and 7) the neurochemical substrate that receives the MEL signal by immunocytochemical methods. These studies should identify the CNS site(s) responsible for the photoperiodic (MEL) control of several seasonal cycles and add to our understanding of how naturally-occurring changes in the environment can have dramatic effects on body fat. The acquisition of the neuroanatomical techniques will compliment the interdisciplinary research program of the Principal Investigator and create a unique research environment for examining brain/behavior/energy metabolism.