Effect of melatonin and diazepam on the dissociated circadian rhythm in rats

Abstract:  The main structures involved in the circadian system in mammals are the suprachiasmatic nuclei (SCN) of the hypothalamus. The SCN contain multiple autonomous single‐cell circadian oscillators that are coupled among themselves, generating a single rhythm. However, under determined circumstances, the oscillators may uncouple and generate several rhythmic patterns. Rats exposed to an artificially established 22‐h light–dark cycle (T22) express two stable circadian rhythms in their motor activity that reflect the separate activities of two groups of oscillators in the morphologically well‐defined ventrolateral and dorsomedial SCN subdivisions. In the experiments described in this paper, we studied the effect of melatonin and diazepam (DZP) administration in drinking water on the dissociated components of rat motor activity exposed to T22, to deduce the possible mechanism of these drugs on the circadian system. In order to suppress the endogenous circadian rhythm of melatonin, in some of the rats the pineal gland or the superior cervical ganglia were removed. The results show that melatonin or DZP treatment increased the manifestation of the light‐dependent component to the detriment of the manifestation of the non‐light‐dependent component and that melatonin, but not DZP, shortens the period of the non‐light‐dependent component. These findings suggest that both DZP and melatonin favor entrainment to external light, and that melatonin could also act on the SCN, producing changes in the period of the circadian cycle.

[1]  J. Redman,et al.  Melatonin administration: effects on rodent circadian rhythms. , 2008, Ciba Foundation symposium.

[2]  M. Vansteensel,et al.  A GABAergic Mechanism Is Necessary for Coupling Dissociable Ventral and Dorsal Regional Oscillators within the Circadian Clock , 2005, Current Biology.

[3]  William J Schwartz,et al.  Forced Desynchronization of Dual Circadian Oscillators within the Rat Suprachiasmatic Nucleus , 2004, Current Biology.

[4]  M. Dubocovich,et al.  Molecular pharmacology, regulation and function of mammalian melatonin receptors. , 2003, Frontiers in bioscience : a journal and virtual library.

[5]  N. Sagiv,et al.  Presynaptic and postsynaptic GABAA receptors in rat suprachiasmatic nucleus , 2003, Neuroscience.

[6]  Y. Touitou,et al.  Effects of Diazepam and Its Metabolites on Nocturnal Melatonin Secretion in the Rat Pineal and Harderian Glands. A Comparative In Vivo and In Vitro Study , 2003, Chronobiology international.

[7]  P. Pévet,et al.  The chronobiotic properties of melatonin , 2002, Cell and Tissue Research.

[8]  P. Zee,et al.  Current understanding of the circadian clock and the clinical implications for neurological disorders. , 2001, Archives of neurology.

[9]  P. Pévet,et al.  In vivo observation of a non-noradrenergic regulation of arylalkylamine N-acetyltransferase gene expression in the rat pineal complex , 2001, Neuroscience.

[10]  A. Kalsbeek,et al.  Melatonin sees the light: blocking GABA‐ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin , 2000, The European journal of neuroscience.

[11]  P. Pévet,et al.  Influence of the Mode of Daily Melatonin Administration on Entrainment of Rat Circadian Rhythms , 1999, Journal of biological rhythms.

[12]  H. Niznik,et al.  Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors , 1999, Nature Neuroscience.

[13]  R Teclemariam-Mesbah,et al.  Anatomical demonstration of the suprachiasmatic nucleus–pineal pathway , 1999, The Journal of comparative neurology.

[14]  Jordi Vilaplana,et al.  Dissociation of the Rat Motor Activity Rhythm Under T Cycles Shorter Than 24 Hours , 1998, Physiology & Behavior.

[15]  Larsen,et al.  Characterization of the multisynaptic neuronal control of the rat pineal gland using viral transneuronal tracing , 1998, The European journal of neuroscience.

[16]  Z. Jiang,et al.  Membrane properties and synaptic inputs of suprachiasmatic nucleus neurons in rat brain slices. , 1997, The Journal of physiology.

[17]  D. Cardinali,et al.  Melatonin Effects on Behavior: Possible Mediation by the Central GABAergic System , 1996, Neuroscience & Biobehavioral Reviews.

[18]  J. Tapia,et al.  Effects of benzodiazepine receptor ligands on isolated rat superior cervical ganglia neurons. , 1996, Pharmacology.

[19]  R. Subbaraj,et al.  Diazepam modulates the period of locomotor rhythm in mice (Mus booduga) and attenuates light-induced phase advances , 1996, Pharmacology Biochemistry and Behavior.

[20]  N. Zisapel,et al.  Reciprocal effects of chronic diazepam and melatonin on brain melatonin and benzodiazepine binding sites , 1996, Journal of pineal research.

[21]  Markus Meister,et al.  Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms , 1995, Neuron.

[22]  J. Herbert,et al.  The Suprachiasmatic Nucleus. The Mind's Clock. , 1994 .

[23]  V. Cassone,et al.  Pinealectomized Rats Entrain and Phase-Shift to Melatonin Injections in a Dose-Dependent Manner , 1993, Journal of biological rhythms.

[24]  R. Reiter,et al.  The melatonin rhythm: both a clock and a calendar , 1993, Experientia.

[25]  R. Moore,et al.  GABA is the principal neurotransmitter of the circadian system , 1993, Neuroscience Letters.

[26]  K. Shimada,et al.  Effects of diazepam administration on melatonin synthesis in the rat pineal gland in vivo. , 1991, Chemical & pharmaceutical bulletin.

[27]  T. Bartness,et al.  Mammalian pineal melatonin: A clock for all seasons , 1989, Experientia.

[28]  M. Menaker,et al.  GABA regulation of circadian responses to light. I. Involvement of GABAA-benzodiazepine and GABAB receptors , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  J. Vanecek,et al.  Hypothalamic melatonin receptor sites revealed by autoradiography , 1987, Brain Research.

[30]  S. Armstrong,et al.  Melatonin phase shifts a mammalian circadian clock , 1987 .

[31]  V. Cassone,et al.  Dose-Dependent Entrainment of Rat Circadian Rhythms by Daily Injection of Melatonin , 1986, Journal of biological rhythms.

[32]  M. Menaker,et al.  Effects of diazepam on circadian phase advances and delays , 1986, Brain Research.

[33]  J. Redman,et al.  Free-running activity rhythms in the rat: entrainment by melatonin. , 1983, Science.

[34]  P. Sokolove,et al.  The chi square periodogram: its utility for analysis of circadian rhythms. , 1978, Journal of theoretical biology.

[35]  R. Reiter.  Morphological studies on the reproductive organs of blinded male hamsters and the effects of pinealectomy or superior cervical ganglionectomy , 1968, The Anatomical record.

[36]  R. A. Hoffman,et al.  Rapid pinealectomy in hamsters and other small rodents , 1965, The Anatomical record.

[37]  Steven M Reppert,et al.  GABA Synchronizes Clock Cells within the Suprachiasmatic Circadian Clock , 2000, Neuron.

[38]  C. K. Song,et al.  SCN cells expressing mt1 receptor mRNA coexpress AVP mRNA in Syrian and Siberian hamsters. , 1999, Advances in experimental medicine and biology.