CNS MELATONIN TARGET SITES--CONTROL OF SEASONAL CYCLES

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The goal of this research is to identify the CNS target sites of melatonin (MEL) that are responsible for the photoperiodic control of seasonal energy balance and reproductive status. The environmental signal for these responses in many species is the change in the daylength, the neuroendocrine transducer of which is the pineal gland and its hormone, melatonin (MEL). MEL only is secreted at night and in this way the duration of secretion encodes the daylength. Thus, 'winter-like' short days (SD) and 'summer-like' long days (LD) are associated with long and short duration MEL signals, respectively. Siberian hamsters will be studied, a species that exhibits dramatic seasonal changes in energy regulation following changes in the photoperiod. Specific Aims (SA) 1: Does destruction of the putative CNS MEL target sites block the reception of MEL signals? the purpose of SA 1 is to identify brain sites involved in the reception/expression of the MEL signals through a process of successive narrowing of the extent and type of destruction of the targeted sites in adult male pinealectomized (PINX) animals challenged with the timed infusion paradigm (TIP) to deliver exogenous MEL signals via the s.c. route of administration. The brain sites that will receive lesions show MEL binding and/or are involved in the integration of metabolic and reproductive responses. A sequence of lesion types will be made: direct current, microknife cut and neurotoxins to destroy cell bodies and fibers of passage, only fibers of passage, and only cell bodies, respectively. Two sets of experiments will be conducted for each brain site in SA 1. In the first, the effects of SD-type inhibitory MEL signals on metabolic and reproductive responses will be tested by giving LD-housed, PINX hamster with or without lesions daily MEL or saline vehicle infusions via the TIP, whereas in the second, the effects of LD- type stimulatory MEL signals on these responses will be tested by giving photoregressed SD-housed, PINX hamsters with or without lesions MEL signals via the TIP. Lesion-induced blockade of either expected set of responses in each experiment will be indicative of a site that is at least responsible partially for the reception/expression of the MEL signal. SA 2: Does stimulation of putative MEL target sites mimic photoperiod change-induced responses? The purpose of SA 2 is to stimulate SD-type responses in PINX LD-housed hamsters, or the return to LD-type responses in SD-housed, photoregressed PINX hamsters via intracerebral MEL infusions at brain sites that show MEL binding and where lesions block the effects of MEL signals in the above experiments. For example, if a lesion blocks MEL-induced, SD-type responses, then only long duration intracerebral MEL infusions will elicit these responses; other types of infusions at the same site will not. The converse should be found for a brain site where lesions block the return to LD-type status by LD MEL signals in SD-housed photoregressed hamsters. These findings should help determine how naturally-occurring changes in the environment can affect energy balance and reproduction.