Physiology & Behavior, Vol. 66, No. 2, pp. 365–370, 1999 © 1999 Elsevier Science Inc. Printed in the USA. All rights reserved 0031-9384/99/$–see front matter PII S0031-9384(98)00309-6 365 Peripheral Heat Loss: A Predictor of the Hypothermic Response to Melatonin Administration in Young and Older Women SAUL S. GILBERT,* CAMERON J. VAN DEN HEUVEL,* DAVID J. KENNAWAY† AND DREW DAWSON 1 * *The University of South Australia, Centre for Sleep Research, The Queen Elizabeth Hospital, Woodville Rd, South Australia, and †The University of Adelaide, Department of Obstetrics and Gynaecology, School of Medicine, Adelaide, South Australia Received 3 August 1998; Accepted 27 October 1998 GILBERT, S. S., C. J. VAN DEN HEUVEL, D. KENNAWAY AND D. DAWSON. Peripheral heat loss: A predic- tor of the hypothermic response to melatonin administration in young and older women. PHYSIOL BEHAV 66(2) 365–370, 1999.—Core hypothermia following daytime melatonin administration typically displays significant interindividual variabil- ity. As this hypothermia has been associated with significant increases in skin temperature, the mechanism by which melato- nin decreases core temperature may involve increasing peripheral heat loss. If so, the interindividual variability in this effect may reflect concomitant interindividual variability in heat loss capacity at the distal periphery. For six younger (mean  SEM: 23.4  0.3 years) and 10 older women (mean  SEM: 65.6  0.7 years), the maximum decrease in core body temperature fol- lowing a 5-mg (p.o.) dose of melatonin was correlated with the capacity to lose heat. This was determined by the maximum increase in contralateral hand temperature following a mild positive thermal challenge (PTC). The regression analysis yielded a significant (p  0.01) correlation of 0.80, suggesting that the individual magnitude of hypothermia following melatonin admin- istration may reflect the capacity of an individual to dissipate heat at the distal periphery. © 1999 Elsevier Science Inc. Thermoregulation Peripheral thermal challenge Core body temperature Soporific Human PREVIOUS research has demonstrated that oral prepara- tions of melatonin ranging from 1.0 to 100 mg have significant core hypothermic effects (4,5,8,17). Although daytime core temperature is typically suppressed by a mean of 0.15–0.3°C (4,5,8,17), significant interindividual variability is evident in this effect [e.g., (5,17)]. Relative to placebo, individual reduc- tions in core temperature ranging from 0.1 to 0.6°C have been documented (17). However, at present, the physiological basis for this variability remains unclear. The homeostatic control of core temperature reflects a dy- namic balance between heat production and heat loss. Broadly speaking, the effectors of heat production are cellular metabolism and muscle activity. On the other hand, passive heat loss is normally controlled by increased cutaneous blood flow and, in more extreme conditions, by the evaporation of sweat (2). An insight into the relationship between heat loss and changes in core temperature has been obtained from work conducted by Achoff [for review, see (1)], and more re- cently by Kräuchi and colleagues (15). These researchers ob- served that, under constant routine, circadian changes in core temperature were associated with inverse temperature changes at distal skin sites including the back of the hands, finger tips and the soles of the feet (15). In contrast, proximal skin sites such as the forehead and trunk displayed concomi- tant temperature changes to that observed in core tempera- ture. Thus, it is possible that distal skin, in particular, may be a major site of heat loss and may mediate the circadian decline in core body temperature. Recent research has demonstrated that, in young subjects, decreases in core temperature following both daytime (5) and evening (14) melatonin administration are association with significant increases in skin temperature. Taken together, these findings suggest that melatonin may reduce core tem- perature by increasing peripheral heat loss, independent of the effects of heat production. If this is the case, the observed interindividual variability in the capacity of melatonin to re- duce core temperature may reflect concomitant interindivid- ual variability in heat loss capacity at the distal periphery. 1 To whom requests for reprints should be addressed. E-mail: drew.dawson@unisa.edu.au