Human melatonin suppression by light: a case for scotopic ef®ciency Mark S. Rea * , John D. Bullough, Mariana G. Figueiro Lighting Research Center, Rensselaer Polytechnic Institute, 21 Union Street, Troy, NY 12180,USA Received 1 November 2000; received in revised form 7 December 2000; accepted 7 December 2000 Abstract Human adult males were exposed to combinations of two illuminances and two spectral power distributions over the course of four nighttime sessions. A dose-dependent response of acute melatonin suppression to light was found, but photopic (cone-based) illuminance did not adequately predict suppression. When melatonin suppression was plotted against scotopic (rod-based) illuminance, the data formed a nearly monotonic function, implicating rods, or a rod- dominated mechanism, in the human melatonin regulation system. The results do not, however, rule out mechanisms other than rods, including novel photoreceptors, as candidates for melatonin regulation in humans. q 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Circadian rhythm; Spectral sensitivity; Photoreceptive system; Pineal response Much is known about the photoreceptors that convert light into neural signals for vision, but the mechanisms for circadian phototransduction are still largely unknown [7]. Since the ®rst report of acute suppression of melatonin by light in humans [4], efforts have been underway to deter- mine the dose-response characteristics and the spectral sensitivity of the ocular channel that mediates pineal response to light. Based on the wealth of information from the literature on human vision [7], conventional wisdom leads to either a photopic (cone, peaking at 555 nm) [10,11] or a scotopic (rod, peaking at 507 nm) [2] hypothesis for circadian phototransduction. Techniques well established in visual psychophysics [9] but unique to studies of circadian spectral sensitivity were used to experimentally contrast the photopic and scotopic hypotheses. These techniques have the major advantage of ef®ciently testing competing hypotheses, but do not elimi- nate more complex models based on unusual combinations of known photoreceptors, nor do they eliminate the possi- bility of novel mechanisms such as cryptochrome [5] or melanopsin [6] in the regulation of melatonin by light. Four adult male subjects (ages 29, 29, 48 and 59 years) participated in this study, which took place on each of ®ve nights (one baseline session and four experimental sessions) in the Clinical Pharmacological Studies Unit of Albany Medical College, Albany, NY. Each session lasted 9 h (from 22:00 to 07:00 h) and subjects were seated at a square, 1.25 £ 1.25 m table throughout the study sessions. The table consisted of a white-painted enclosure containing 16 ¯uor- escent lamps, eight each of two correlated color tempera- tures: 3000 K (Philips F40SPEC30, `warm') and 7500 K (Philips F40C75, `cool'). The lamps were mounted in alter- nating sockets and controlled by electronic dimming ballasts (Lutron) and photocells so that the light output of each set of eight lamps could be independently controlled and mixed together. A clear piece of glass and an acrylic diffuser were mounted over the enclosure and served as the tabletop. When subjects sat around the table, the lamps and diffuser provided uniform illumination at the subjects' eyes. During the study, when the ¯uorescent lamps were switched on, subjects read material printed onto overhead projector transparency sheets so that they received a controlled dose of light exposure while reading. All subjects followed their normal daily routine and refrained from consuming caffeine for 12 h before each session, which always began at 22:00 h. Upon arrival at the study location, a nurse or physician inserted a catheter into a vein of each subject. Starting at 45 min after each hour, blood samples (3 ml) were drawn from each subject in a ®xed order. Samples were spun in a refrigerator centri- fuge at 2300 rev./min for 10 min and separated plasma was frozen at 2868C. Frozen samples were sent to an indepen- Neuroscience Letters 299 (2001) 45±48 0304-3940/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(01)01512-9 www.elsevier.com/locate/neulet * Corresponding author. Tel.: 11-518-687-7100; fax: 11-518- 687-7120. E-mail address: ream@rpi.edu (M.S. Rea).