MELATONIN IN THE CNS: REGULATION OF BEHAVIORAL CYCLES

我研究的长期目标是了解

The long-term objective of my research is to understand the neuroendocrine control of sexual behavior and the mechanism that regulate its expression throughout the year. Most mammals, including humans, express daily and yearly cycles in physiological and behavioral processes. Animal models have proven extremely useful in studying the neural and endocrine bases of these rhythmics. The Syrian hamster (Mesocricetus auratus) has been extensively investigate because its annual cycles can be experimentally manipulated under laboratory conditions. Increases and decreases in day length (photoperiod) that are characteristic of the changing seasons drive the hamster through annual cycles of reproductive stimulation and inhibition. These cycles are reflected in fluctuating levels of circulating hormones, drastic changes in reproductive organ morphology and function, and altered potential for sexual and other behaviors. Both the endocrine and behavioral responses to changing day lengths require the pineal gland and its nocturnal secretion of the hormone, melatonin. Much is known about the effect of day length on the generation of the melatonin signal each night, but the neuroendocrine processes that respond to melatonin and result in altered reproductive potential are not well understood. Melatonin binding sites in the central nervous system have been characterized pharmacologically and their location has been determined by in vitro autoradiography using I-melatonin as ligand. Melatonin binding sites have been found in numerous areas throughout the brain, yet very little is known about which site or sites are relevant for mediating the effects of melatonin in the transduction of day length information. The experiments proposed in this application use both males and females, and they emphasize behavior. Melatonin will be administered to pinealectomized hamsters using procedures that control the amplitude, duration, and timing of the melatonin signal. A unique microdialysis infusion system will be employed to deliver melatonin into localized regions of the brain that contain melatonin binding sites. The capacity for these site to respond to melatonin and there by convey relevant information to photoperiodic response systems will be evaluated. Studies with the male hamster will investigate photoperiodic influence on both behavioral and endocrine system and will determine whether the same or different melatonin sites are relevant to each. Studies with the female relevance of individual melatonin binding sites to each behavioral response. These experiments will not only greatly expand our knowledge of seasonal reproductive cycles, but will also provide new insights into the interaction of internal and external variables and their regulation of behavioral potential.