The Institute of Physiology of the Czech Academy of Sciences (CAS) has been involved in the field of chronobiology, i.e., in research on temporal regulation of physiological processes, since 1970. The review describes the first 35 years of the research mostly on the effect of light and daylength, i.e., photoperiod, on entrainment or resetting of the pineal rhythm in melatonin production and of intrinsic rhythms in the central biological clock. This clock controls pineal and other circadian rhythms and is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. During the early chronobiological research, many original findings have been reported, e.g. on mechanisms of resetting of the pineal rhythm in melatonin production by short light pulses or by long exposures of animals to light at night, on modulation of the nocturnal melatonin production by the photoperiod or on the presence of high affinity melatonin binding sites in the SCN. The first evidence was given that the photoperiod modulates functional properties of the SCN and hence the SCN not only controls the daily programme of the organism but it may serve also as a calendar measuring the time of a year. During all the years, the chronobiological community has started to talk about "the Czech school of chronobiology". At present, the today´s Laboratory of Biological Rhythms of the Institute of Physiology CAS continues in the chronobiological research and the studies have been extended to the entire circadian timekeeping system in mammals with focus on its ontogenesis, entrainment mechanisms and circadian regulation of physiological functions. Key words: Pineal, Melatonin, AA-NAT rhythm, Light entrainment, Photoperiod, SCN clock.

• MeSH
• Academies and Institutes MeSH
• Biological Clocks physiology   MeSH
• Circadian Clocks physiology   MeSH
• Circadian Rhythm * physiology   MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Pineal Gland * metabolism   physiology   MeSH
• Photoperiod MeSH
• Humans MeSH
• Melatonin metabolism   MeSH
• Brain metabolism   physiology   MeSH
• Suprachiasmatic Nucleus physiology   metabolism   MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH
• Names of Substances
• Melatonin MeSH

BACKGROUND AND PURPOSE: Opioids affect the circadian clock and may change the timing of many physiological processes. This study was undertaken to investigate the daily changes in sensitivity of the circadian pacemaker to an analgesic dose of morphine, and to uncover a possible interplay between circadian and opioid signalling. EXPERIMENTAL APPROACH: A time-dependent effect of morphine (1 mg·kg(-1) , i.p.) applied either during the day or during the early night was followed, and the levels of phosphorylated ERK1/2, GSK3β, c-Fos and Per genes were assessed by immunohistochemistry and in situ hybridization. The effect of morphine pretreatment on light-induced pERK and c-Fos was examined, and day/night difference in activity of opioid receptors was evaluated by [(35) S]-GTPγS binding assay. KEY RESULTS: Morphine stimulated a rise in pERK1/2 and pGSK3β levels in the suprachiasmatic nucleus (SCN) when applied during the day but significantly reduced both kinases when applied during the night. Morphine at night transiently induced Period1 but not Period2 in the SCN and did not attenuate the light-induced level of pERK1/2 and c-Fos in the SCN. The activity of all three principal opioid receptors was high during the day but decreased significantly at night, except for the δ receptor. Finally, we demonstrated daily profiles of pERK1/2 and pGSK3β levels in the rat ventrolateral and dorsomedial SCN. CONCLUSIONS AND IMPLICATIONS: Our data suggest that the phase-shifting effect of opioids may be mediated via post-translational modification of clock proteins by means of activated ERK1/2 and GSK3β.

• MeSH
• Circadian Clocks drug effects   MeSH
• Period Circadian Proteins metabolism   MeSH
• Circadian Rhythm drug effects   MeSH
• Phosphorylation drug effects   MeSH
• Glycogen Synthase Kinase 3 metabolism   MeSH
• Glycogen Synthase Kinase 3 beta MeSH
• Rats MeSH
• Mitogen-Activated Protein Kinase 1 metabolism   MeSH
• Mitogen-Activated Protein Kinase 3 metabolism   MeSH
• Mitogen-Activated Protein Kinases metabolism   MeSH
• Morphine pharmacology   MeSH
• Suprachiasmatic Nucleus drug effects   metabolism   MeSH
• Rats, Wistar MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Period Circadian Proteins MeSH
• Gsk3b protein, rat MeSH Browser
• Glycogen Synthase Kinase 3 MeSH
• Glycogen Synthase Kinase 3 beta MeSH
• Mitogen-Activated Protein Kinase 1 MeSH
• Mitogen-Activated Protein Kinase 3 MeSH
• Mitogen-Activated Protein Kinases MeSH
• Morphine MeSH
• Per1 protein, rat MeSH Browser