© 2007 The Authors Doi: 10.1111/j.1742-7843.2006.00032.x Journal compilation © 2007 Nordic Pharmacological Society . Basic & Clinical Pharmacology & Toxicology , 100, 258–268 Blackwell Publishing, Ltd. Orally Administered Melatonin Improves Nocturnal Rest in Young and Old Ringdoves ( Streptopelia risoria) Sergio D. Paredes 1 , M a Pilar Terrón 1 , Vicente Valero 1 , Carmen Barriga 1 , Russel J. Reiter 2 and Ana B. Rodríguez 1 1 Department of Physiology, Faculty of Science, University of Extremadura, Badajoz, Spain, and 2 Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA (Received September 26, 2006; Accepted November 1, 2006) Abstract: Melatonin possesses chronobiotic properties, which affects sleep/wake rhythms. We investigated a 7-day admin- istration of melatonin (0.25, 2.5 and 5 mg/ kg body weight) on the activity/rest rhythms of a diurnal animal (the ringdove, Streptopelia risoria), aged 2–3 (young) and 10–12 (old) years, and its possible relationship with the serum levels of melatonin and serotonin. Total nocturnal and diurnal activity pulses were logged at basal, during, and up to 7 days after the treatments. The animals received 0.1 ml of melatonin orally 1 hr before lights off. The results showed that the administra- tion of whichever melatonin dose decreased both diurnal and nocturnal old ringdove activity, the reduction being larger at night. The young animals also reduced their nocturnal activity with all three melatonin concentrations, whereas their diurnal activity only decreased with the 2.5 and 5 mg/kg body weight treatments. We chose those treatments that gave the best results in terms of nocturnal rest and the least affected diurnal activity (0.25 mg /kg body weight and 2.5 mg /kg in the young and old animals, respectively). Serum melatonin was measured by radioimmunoassay and serotonin by ELISA. In both age groups, the treatment increased both nocturnal and diurnal melatonin levels, with the effect continuing until 1 day after the last dose. Serum serotonin levels were unaffected by the treatments in either age group. The treatment restored the amplitude of the serum melatonin rhythm in the old animals to that of the young group. In summary, treatment with melatonin may be appropriate to improve nocturnal rest, and beneficial as a therapy for sleep disorders. Melatonin is released from the pineal gland in close associ- ation with the light–dark cycle. Melatonin has been implicated in a number of physiological functions including regulation of the sleep/wake cycle and other circadian and seasonal rhythms, body temperature and synchronization of various circadian neuroendocrine processes [1–9]. Among these varied functions, sleep/wake rhythm promoting functions of melatonin have gained wide scientific attention because of its ability to provide relief from sleeplessness [10] and the temporal relationship between the nocturnal rise in the secretion of the indolamine and the ‘opening of the sleep gate’ at night [11]. In parallel, serotonin is known to increase the quality of slow wave sleep [12], as well as being a waking neurotransmitter [13]. In addition, the close relationship between serotonergic activity and the adjustments of circadian phase has suggested that serotonin also plays a role in the endogenous regulation of the circadian clock [14]. With age, some aspects of the sleep–wake cycle undergo well-known changes, such as shallower nocturnal sleep with more arousals, less slow wave sleep, prevalence of daytime naps [15,16], impaired sleep consolidation and less stability of sleep [17], a characteristic decline in sleep efficiency and total sleep time, and a marked fragmentation of the sleep–wake cycle [11]. Decline in pineal serotonin during ageing [18], age-dependent decline in the level of circulating melatonin and age-dependent increase in the rate of insomnia [19] have also been reported. It has been suggested that the decline in melatonin secretion with age is one of the major reasons for increased sleep disruption in older people [11,20], with corre- lations being found between age-related disturbances in the sleep/wake cycle and decrease in the melatonin output [21,22], advance in the acrophase of melatonin secretion [23], and reduction in the amplitude of the melatonin rhythm [24,25]. Different studies have shown that exogenous melatonin exerts direct (hypnotic) and circadian effects on sleep [26]. The dual activity of melatonin makes it useful for the treat- ment of circadian rhythm sleep disorders [11,27,28]. Thus, melatonin therapy corrects some changes in the sleep–wake pattern in older people, although it also corrects problems of sleep in younger insomniacs [29]. While the effect of exogenous melatonin on the circadian system in nocturnal species has been extensively studied, little is known about its chronobiotic effect in diurnally active and monophasic species, such as most birds. It has been suggested that melatonin has a physiological role in the cir- cadian synthesis and release of serotonin and that the exog- enous administration of melatonin may affect the circadian rhythm of this neurotransmitter [30]. Hence, the aim of the present work was to investigate the effect of oral administra- tion of melatonin at concentrations of 0.25, 2.5 and 5 mg / kg body weight on the activity/rest rhythms of both young and old ringdove, Streptopelia risoria, monophasic, diurnal and Author for correspondence: Ana B. Rodríguez, Department of Physiology, Faculty of Science, University of Extremadura, Avda de Elvas, S/N, 06071, Badajoz, Spain (fax +34 924 289 388, e-mail moratino@unex.es).