Research report Entrainment of locomotor activity rhythm in pinealectomized adult Syrian hamsters by daily melatonin infusion Sandrine Schuhler, Bruno Pitrosky, Raymond Kirsch, Paul Pe ´ vet * Lab. De Neurobiologie des Fonctions Rythmiques et Saisonnie `res, Universite ´ Louis Pasteur, 12 rue de l’Universite ´, UMR CNRS 7518, F-67000 Strasbourg, France Received 17 July 2001; received in revised form 15 January 2002; accepted 15 January 2002 Abstract Melatonin entrains circadian rhythms in several species of rodents, but a role for melatonin as a Zeitgeber in the adult Syrian hamster is debated. The aim of this study was to define the conditions of daily programmed melatonin infusion in which an entrainment of the locomotor activity rhythm is obtained in adult male Syrian hamsters. The animals were pinealectomized, cannulated with a subcutaneous infusion system and submitted to dim red light conditions. They were initially daily infused with vehicle until free-running was established. Then, the animals were divided into three experimental groups, each group corresponding to a specific melatonin dose and infusion duration: (1) 10 mg melatonin/h for 5 h; (2) 30 mg melatonin/h for 5 h; and (3) 50 mg melatonin/h for 1 h. Of the total 64 hamsters, 37 hamsters fully entrained to the melatonin infusion regardless of whether the animals expressed during pre-treatment a free-running period (t ) B/ or !/24 h, 20 animals presented a transient entrainment and seven did not entrain. Of the 37 animals entrained, withdrawal of melatonin re-established free-running rhythms, although often with a different t compared with that observed during pre-treatment. These results indicate that after a long time of daily infusion, melatonin is able to entrain the free-running rhythm in adult Syrian hamster. The mechanism involved is not known, but the change in t observed after melatonin treatment in some animals suggests that melatonin, directly or indirectly, affects the functioning of the clock. # 2002 Elsevier Science B.V. All rights reserved. Keywords: Syrian hamster; Circadian rhythm; Entrainment; Melatonin 1. Introduction Melatonin secretion represents an endocrine signal which in several mammalian species plays a role in the control of seasonal reproduction [5,20]. Moreover, melatonin administered daily by subcutaneous injection [24], infusion [21], or via the drinking water [29] synchronizes circadian rhythms of locomotor activity or body temperature in rats kept in constant darkness (DD). The entraining effect of the hormone is dose- dependent [7,34], and under daily acute administration, entrainment occurs when there is coincidence between activity onset and MEL onset [24,21]. The phase response curve (PRC) obtained in the rat by single melatonin injection [2] shows maximum phase-advances of approximately 30  /40 min at circadian time (CT) 10 / 12 (CT 12 being the time of locomotor activity onset). This effect could be the consequence of an action of melatonin on the clock since melatonin receptors have been detected in this structure (review in [18]). The Syrian hamster is also sensitive to the entraining effect of melatonin when administrated prenatally and early postnatally. Indeed, daily injection to pregnant Syrian hamsters for 7 days prenatally synchronizes the phase of activity onset of the new-born hamsters during 3 weeks [10]. In addition, daily melatonin injection from postnatal days 1  /5 entrains hamster pups, but this effect is not observed from postnatal days 6  /10 or 21  /25 [15]. In the adult Syrian hamster, a role for melatonin as a chronobiological agent is under debate. Melatonin injections at CT 8 and CT 10 cause phase-advances, but such phase-changes also occur after vehicle injec- tions [16]. Thus, handling artifacts probably underlie these phase-shifts since Hastings et al. [16] were unable * Corresponding author. Tel.: 33-390-240506; fax: 33-390- 240528 E-mail address: pevet@neurochem.u-strasbg.fr (P. Pe ´ vet). Behavioural Brain Research 133 (2002) 343 /350 www.elsevier.com/locate/bbr 0166-4328/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved. PII:S0166-4328(02)00017-7