This study examines the effect of light pulses and administration of the pineal hormone melatonin on the circadian activity rhythm of C3H/HeN mice. Mice were housed in constant dark in cages equipped with running wheels. Phase shifts in the circadian rhythm of wheel-running activity were measured following treatment with a 15-min pulse of light (300 lux) or administration of vehicle (ethanol/saline) or melatonin (90 μg, sc). Light treatment induced phase changes in circadian activity rhythms; specifically, delays during early subjective night (circadian time [CT] 12.5 to CT 18.5) and advances during late subjective night (CT 0.5). A single dose of melatonin administered at various CTs had no consistent effect on free-running circadian activity rhythms. By contrast, melatonin administration for 3 consecutive days at the same clock time induced advances in circadian activity rhythms by more than 1 h when the first dose was administered at CT 10 and induced delays in circadian activity rhythms by up to 1 h when the first dose was administered between CT 24 and CT 2. With the caveat that multi- ple melatonin treatments are required to induce phase shifts, the results suggest that the circadian timing system controlling the rhythm of wheel-running activity in the C3H/HeN mouse is responsive to both light and melatonin.
Aguilar-Roblero R. and Vega-González A. (1993) Splitting of locomotor circadian rhythmicity in hamsters is facilitated by pinealectomy. Brain Res605:229-236.
2.
Armstrong Sm (1991a) Entrainment of vertebrate circadian rhythms by melatonin. In Advances in Pineal Research, A Foldes and RJ Reiter, eds, vol 5, pp 259-266, J. Libbey, London.
3.
Armstrong Sm (1991b) Treatment of sleep disorders by melatonin administration . In Advances in Pineal Research, A Foldes and RJ Reiter, eds, vol 6, pp 263-274, J. Libbey, London.
4.
Armstrong Sm, Thomas Emv, and Chesworth Mj (1989) Melatonin induced phase-shifts of rat circadian rhythms. In Advances in Pineal Research, D Evered and S Clark, eds, pp 188-207, Pittman, London.
5.
Aschoff J. (1979) Circadian rhythms: Influences of internal and external factors on the period measured in constant conditions. Z Tierpsychol49:225-249.
6.
Bartness Tj, Powers Jb, Hastings Mh, Bittman El, and Goldman Bd (1993) The timed infusion paradigm for melatonin delivery: What has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses?J Pineal Res15:161-190.
7.
Benloucif S. and Dubocovich Ml (1994) Individual differences in reentrainment correlate with specific 2-[125I]-iodomelatonin (2-IMEL) binding in the suprachiasmatic nucleus of C3H/HeN mice. Soc Neurosci Abstr20:1438.
8.
Benloucif S., Masana Mi, and Dubocovich Ml (1995) Reduced circadian responses to light in aged C3H/HeN mice. Soc Neurosci Abstr21:1235.
9.
Benloucif S., Niblick Mj, and Dubocovich Ml (1993) Melatonin attenuates light-induced phase shifts in circadian activity in C3H/HeN mice. Soc Neurosci Abstr19:1815.
10.
Broadway J., Arendt J., and Folkard S. (1987) Bright light phase shifts the human melatonin rhythm during the Antarctic winter. Neurosci Lett79:185-189.
11.
Brooks Ds and Cassone Vm (1992) Daily and circadian regulation of 2-[125 I]iodomelatonin binding in the chick brain. Endocrinology131:1297-1304.
12.
Burešová M., Benešová O., and Illnerová H. (1990) Aging alters resynchronization of the circadian system in rats after a shift of the light-dark cycle. Experientia46:75-77.
13.
Cassone Vm (1990) Effects of melatonin on vertebrate circadian systems . TINS13:457-464.
14.
Cassone Vm (1992) The pineal gland influences rat circadian activity rhythms in constant light. J Biol Rhythms7:27-40.
15.
Cassone Vm, Chesworth Mj, and Armstrong Sm (1986) Entrainment of rat circadian rhythms by daily injection of melatonin depends upon the hypothalamic suprachiasmatic nucleus . Physiol Behav36:1111-1121.
16.
Cassone Vm, Roberts Mh, and Moore Ry (1988) Effects of melatonin on 2-deoxy-[1-14C] glucose uptake within rat suprachiasmatic nucleus. Am J Physiol (Reg Integr Comp Physiol)255:R332-R337.
17.
Cheung Pw and McCormack Ce (1982) Failure of pinealectomy or melatonin to alter circadian activity rhythm of the rat. Am J Physiol (Reg Integr Comp Physiol)242:R261-R264.
18.
Daan S. and Pittendrigh Cs (1976) A functional analysis of circadian pacemakers in nocturnal rodents. II. The variability of phase response curves. J Comp Physiol106:253-266.
19.
Davis Fc and Mannion J. (1988) Entrainment of hamster pup circadian rhythms by prenatal melatonin injections to the mother. Am J Physiol255:R439-R448.
20.
DeCoursey Pj (1961) Effect of light on the circadian activity rhythm of the flying squirrel, Glaucomys volans. Z Vergl Physiol44:331-354.
21.
Dubocovich Ml, Benloucif S., and Masana Mi (1996) Melatonin receptors in the mammalian suprachiasmatic nucleus. Behav Brain Res73:141-147.
22.
Ebihara S., Hudson Dj, Marks T., and Menaker M. (1986) Genetic control of melatonin synthesis in the pineal gland of the mouse. Science231:491-493.
23.
Finkelstein Js, Baum Fr, and Campbell Cs (1978) Entrainment of the female hamster to reversed photoperiod: Role of the pineal. Physiol Behav21:105-111.
24.
Foley Pb, Caimcross Kd, and Foldes A. (1986) Pineal indoles: Significance and measurement. Neurosci Biobehav Rev10:273-293.
25.
Garfinkel D., Laudon M., Nof D., and Zisapel N. (1995) Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet346:541-544.
26.
Gauer F., Masson-Pevet M., Stehle J., and Pevet P. (1994a) Daily variations in melatonin receptor density of rat pars tuberalis and suprachiasmatic nuclei are distinctly regulated . Brain Res641:92-98.
27.
Gauer F., Masson-Pevet M., and Pevet P. (1994b) Differential regulation of melatonin receptors by short- versus long-term pinealectomy in the suprachiasmatic nuclei and pars tuberalis. J Pineal Res16:73-76.
28.
Gillette Mu and McArthur Aj (1996) Circadian actions of melatonin at the suprachiasmatic nucleus. Behav Brain Res73:135-139.
29.
Golombek Da, Escolar E., and Cardinali Dp (1991) Melatonin-induced depression of locomotor activity in hamsters: Time-dependency and inhibition by the central-type benzodiazepine antagonist Ro 15-1788. Physiol Behav49:1091-1097.
30.
Goto M., Oshima I., Tomita T., and Ebihara S. (1989) Melatonin content of the pineal gland in different mouse strains. J Pineal Res7:195-204.
31.
Hastings Jw and Sweeney Bm (1958) A persistent diurnal rhythm of luminescence in Gonyaulax polyedra. Biol Bull115:440-458.
32.
Hastings Mh, Mead Sm, Vindlacheruvu Rr, Ebling Fj, Maywood Es, and Grosse J. (1992) Non-photic phase shifting of the circadian activity rhythm of Syrian hamsters: The relative potency of arousal and melatonin . Brain Res591:20-26.
33.
Hazlerigg Dg, Gonzalez-Brito A., Lawson W., Hastings Mh, and Morgan Pj (1993) Prolonged exposure to melatonin leads to time-dependent sensitization of adenylate cyclase and down-regulates melatonin receptors in pars tuberalis cells from ovine pituitary 132:285-292.
34.
Humlova M. and Illnerova H. (1990) Melatonin entrains the circadian rhythm in the rat pineal N-acetyltransferase activity. Neuroendocrinology52:196-199.
35.
Kincl Fa, Chang Cc, and Zluzkova V. (1970) Observation on the influence of changing photoperiod on spontaneous wheel-running activity of neonatally pinealectomized rats . Endocrinology87:38-42.
36.
Klein Dc and Moore Ry (1979) Pineal N-acetyltransferase and hydroxyindole-0-methyltransferase: Control by the retinohypothalamic tract and the suprachiasmatic nucleus. Brain Res174:245-262.
37.
Krause D. and Dubocovich Ml (1990) Regulating sites on the melatonin system of mammals . TINS13:82-95.
38.
Laitinen Jt, Castren E., Vakkuri O., and Saavedra Jm (1989) Diurnal rhythm of melatonin binding in the rat suprachiasmatic nucleus. Endocrinology124:1585-1587.
39.
Lewy Aj, Ahmed S., Latham-Jackson JM, and Sack RL (1992) Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int9:380-392.
40.
Lewy Aj, Sack Rl, Miller S., and Hoban Tm (1987) Antidepressant and circadian phase-shifting effects of light. Science235:352-354.
41.
Lynch Hj, Ho M., and Wurtman Rj (1977) The adrenal medulla may mediate the increase in pineal melatonin synthesis induced by stress, but not that caused by exposure to darkness. J Neural Trans40:87-97.
42.
Margraf Rr and Lynch Gr (1993) An in vitro circadian rhythm of melatonin sensitivity in the suprachiasmatic nucleus of the Djungarian hamster, Phodopus sungorus. Brain Res609:45-50.
43.
Masana Mi, Benloucif S., and Dubocovich Ml (1995) Circadian variations in melatonin receptor density in the suprachiasmatic nucleus (SCN) of C3H/HeN mice. Soc Neurosci Abstr21:184.
44.
Mason R. and Brooks A. (1988) The electrophysiological effects of melatonin and a putative melatonin antagonist (N-acetyltryptamine) on rat suprachiasmatic neurons in vitro. Neurosci Lett95:296-301.
45.
McArthur Aj, Gillette Mu, and Prosser Ra (1991) Melatonin directly resets the rat suprachiasmatic circadian clock in vitro. Brain Res565:158-161.
46.
Mead S., Ebling Fjp, Maywood Es, Humby T., Herbert J., and Hastings Mh (1992) A nonphotic stimulus causes instantaneous phase advances of the light-entrainable circadian oscillator of the Syrian hamster but does not induce the expression of c-fos in the suprachiasmatic nuclei . J Neurosci12:2516-2522.
47.
Miller Jd (1993) On the nature of the circadian clock in mammals . Am J Physiol (Reg Integr Comp Physiol)264:R821-R832.
48.
Oakley Ng, Skingle M., and Hagan Rm (1993) The time-dependency of the acute effects of melatonin on spontaneous locomotor activity in the rat. Paper presented at the Sixth Colloquium of the European Pineal Society, Copenhagen.
49.
Oldani A., Ferini-Strambi L, Zucconi M., Stankov B., Fraschini F., and Smirne S. (1994) Melatonin and delayed sleep phase syndrome: Ambulatory polygraphic evaluation . Neuro-Report6:132-134.
50.
Petrie K., Dawson Ag, Thompson L., and Brook R. (1993) A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatry33:526-530.
51.
Pickard Ge and Turek Fw (1983) The hypothalamic paraventricular nucleus mediates the photoperiodic control of reproduction but not the effects of light on the circadian rhythm of activity. Neurosci Lett43:67-72.
52.
Pittendrigh Cs and Daan S. (1976) A functional analysis of circadian pacemakers in nocturnal rodents. I. The stability and lability of spontaneous frequency. J Comp Physiol106:223-252.
53.
Puchalski W. and Lynch Gr (1988) Daily melatonin injections affect the expression of circadian rhythmicity in Djungarian hamsters kept under a long-day photoperiod . Neuroendocrinology48:280-286.
54.
Quay Wb ( 1968) Individualization and lack of pineal effect in the rat's circadian locomotor rhythm. Physiol Behav3:109.
55.
Quay Wb ( 1970) Precocious entrainment and associated characteristics of activity patterns following pinealectomy and reversal of photoperiod. Physiol Behav5:1281-1290.
56.
Redman Jr and Armstrong S. (1988) Reentrainment of rat circadian activity rhythms: Effects of melatonin. J Pineal Res5:203-215.
57.
Redman Jr, Armstrong S., and Ng Kt (1983) Free-running activity rhythms in the rat: Entrainment by melatonin. Science219:1089-1091.
58.
Reiter Rj (1987) The melatonin message: Duration versus coincidence hypotheses. Life Sci40:2119-2131.
59.
Reiter Rj (1991) Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocrinol Rev12:151-180.
60.
Reppert Sm, Weaver Dr, and Ebisawa T. (1994) Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron13:1177-1185.
61.
Reppert Sm, Weaver Dr, Rivkees Sa, and Stopa Eg (1988) Putative melatonin receptors in a human biological clock. Science242:78-81.
62.
Rusak B. and Yu G-D. (1993) Regulation of melatonin-sensitivity and firing-rate rhythms of hamster suprachiasmatic nucleus neurons: Pinealectomy effects. Brain Res602:200-204.
63.
Sack Rl, Blood Ml, and Lewy Aj (1992) Melatonin rhythms in night shift workers. Sleep15:434-441.
64.
Sack Rl, Lewy Aj, Blood Ml, Stevenson J., and Keith Ld (1991) Melatonin administration to blind people: Phase advances and entrainment. J Biol Rhythms6:249-261.
65.
Schwartz Wj and Zimmerman P. (1990) Circadian timekeeping in BALB/c and C57BL/6 inbred mouse strains. J Neurosci10:3685-3694.
66.
Shibata S., Cassone Vm, and Moore Ry (1989) Effects of melatonin on neuronal activity in the rat suprachiasmatic nucleus in vitro. Neurosci Lett97:140-144.
67.
Siuciak Ja, Fang Jm, and Dubocovich Ml (1990) Autoradiographic localization of 2-[125 I]-iodomelatonin binding sites in the brains of C3H/HeN and C57BL/6J strains of mice. Eur J Pharmacol180:387-390.
68.
Smith Rd, Turek Fw, and Takahashi Js (1992) Two families of phase-response curves characterize the resetting of the hamster circadian clock. Am J Physiol (Reg Integr Comp Physiol)262:R1149-R1153.
69.
Stehle J., Vanecek J., and Vollrath L. (1989) Effects of melatonin on spontaneous electrical activity of neurons in rat suprachiasmatic nuclei: An in vitro iontophoretic study. J Neural Trans (Gen Sect)78:173-177.
70.
Stetson Mh, Sarafidis E., and Rollag Md (1986) Sensitivity of adult male Djungarian hamsters (Phodopus sungorus sungorus) to melatonin injections throughout the day: Effects on the reproductive system and the pineal. Biol Reprod35:618-623.
71.
Tamarkin L., Baird Cj, and Almeida Ofx (1985) Melatonin: A coordinating signal for mammalian reproduction? Science227:714-725.
72.
Tenn C. and Niles Lp (1993) Physiological regulation of melatonin receptors in rat suprachiasmatic nuclei: Diurnal rhythmicity and effects of stress . Molec Cell Endocrinol98:43-48.
73.
Underwood Hj (1986) Circadian rhythms in lizards: Phase response curve for melatonin. J Pineal Res3:187-196.
74.
Vanecek J. and Illnerová H. (1982) Night pineal N-acetyltransferase activity in rats exposed to white or red light pulses of various intensity and duration. Experientia38:1318-1320.
75.
Van Reeth O., Olivares Y., Zhang Fw, Turek Fw, Defrance R., and Mocaer E. (1994) S-20098, a melatonin-agonist, phase shifts the circadian clock of mice and syrian hamsters according to a phase-response-curve . Soc Neurosci Abstr20:1440.
76.
Warren Ws, Hodges Db, and Cassone Vm (1993) Pinealectomized rats entrain and phase-shift to melatonin injections in a dose-dependent manner. J Biol Rhythms8:233-245.
77.
Weaver Dr and Reppert Sm (1986) Maternal melatonin communicates daylength to the fetus in Djungarian hamsters. Endocrinology119:2861-2863.
78.
Yellon Sm and Hilliker S. (1994) Influence of acute melatonin treatment and light on the circadian melatonin rhythm in the Djungarian hamster. J Biol Rhythms9:71-81.
79.
Zaidan R., Geoffriau M., Brun J., Taillard J., Bureau C., Chazot G., and Claustrat B. (1994) Melatonin is able to influence its secretion in humans: Description of a phase-response curve. Neuroendocrinology60:105-112.
