THE TIMED INFUSION PARADIGM FOR MELATONIN DELIVERY - WHAT HAS IT TAUGHT US ABOUT THE MELATONIN SIGNAL, ITS RECEPTION, AND THE PHOTOPERIODICCONTROL OF SEASONAL RESPONSES

This review summarizes the evidence showing that the duration of the n octurnal secretory profile of pineal melatonin (MEL) is critical for e liciting seasonally appropriate reproductive physiological and behavio ral responses in mammals. We review experiments using the timed infusi on paradigm (TIP) to deliver MEL either systemically or centrally to p inealectomized hamsters and sheep. In this paradigm, MEL is infused, u sually once daily, for a specific number of hours and at a predetermin ed time of day. This experimental strategy tests most directly those f eatures of the MEL signal that are necessary to trigger photoperiodic responses. The data suggest that the duration of the MEL stimulation i s the critical feature of die MEL signal for both inhibitory and stimu latory effects of the hormone on the photoperiodic control of reproduc tive development in juvenile Siberian hamsters, and for the photoperio dic control of reproductive and metabolic responses in adult Siberian and Syrian hamsters and sheep. The use of the TIP reveals the importan ce of the frequency of die signal presentation of MEL and suggests the importance of a period of low-to-absent circulating concentrations of the hormone. The TIP also reveals that die characteristics of the MEL signal that regulate male sexual behavior are similar to those that a re critical for reproductive and metabolic responses in Syrian hamster s. We summarize the locations of possible functional MEL target sites identified by combining the TIP with traditional brain lesion techniqu es. Evidence from such studies suggests that the integrity of the supr achiasmatic nucleus (SCN) region in Siberian hamsters and the anterior hypothalamus in Syrian hamsters is necessary for the response to shor t-day MEL signals. The TIP has been used to deliver MEL to putative ta rget sites for the hormone in the brain of juvenile and adult Siberian hamsters. The results of these preliminary experiments suggest that d ie regions of specific MEL binding in this species, especially the SCN , are effective sites where MEL may stimulate short-day-type responses . In contrast, results from intracranial application of MEL in sheep s uggest the medial basal hypothalamus as a critical site of action. Fin ally, we also discuss potential applications of the TIP for identifica tion of brain MEL target sites, understanding of other photoperiodic p henomena and responses, and resolution of the cellular/molecular basis underlying the reception and interpretation of MEL signals. It is our collective view that die TIP has played, and will continue to play, a pivotal role in elucidation of the function of MEL in the photoperiod ic control of seasonal mammalian responses and that die duration of th e MEL signal is the critical parameter of die nocturnal secretion prof ile of the hormone for the photoperiodic control of several seasonally adaptive responses in mammalian species as diverse as hamsters and sh eep.