scholarly journals Neural Mechanisms of Circadian Regulation of Natural and Drug Reward

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Lauren M. DePoy ◽  
Colleen A. McClung ◽  
Ryan W. Logan
Keyword(s):  
Circadian Rhythms ◽  
Drugs Of Abuse ◽  
Neural Circuitry ◽  
Circadian System ◽  
Neural Mechanisms ◽  
Drug Reward ◽  
Reward Function ◽  
Timing System ◽  
Circadian Timing System ◽  
Negative Health Outcomes

Circadian rhythms are endogenously generated near 24-hour variations of physiological and behavioral functions. In humans, disruptions to the circadian system are associated with negative health outcomes, including metabolic, immune, and psychiatric diseases, such as addiction. Animal models suggest bidirectional relationships between the circadian system and drugs of abuse, whereby desynchrony, misalignment, or disruption may promote vulnerability to drug use and the transition to addiction, while exposure to drugs of abuse may entrain, disrupt, or perturb the circadian timing system. Recent evidence suggests natural (i.e., food) and drug rewards may influence overlapping neural circuitry, and the circadian system may modulate the physiological and behavioral responses to these stimuli. Environmental disruptions, such as shifting schedules or shorter/longer days, influence food and drug intake, and certain mutations of circadian genes that control cellular rhythms are associated with altered behavioral reward. We highlight the more recent findings associating circadian rhythms to reward function, linking environmental and genetic evidence to natural and drug reward and related neural circuitry.

Circadian rhythms, sleep, and anti-cancer treatments

2018 ◽  
Author(s):  
Pasquale F. Innominato ◽  
David Spiegel
Keyword(s):  
Quality Of Life ◽  
Circadian Rhythms ◽  
Biological Functions ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Timing System ◽  
Physical Wellbeing ◽  
Circadian Timing System ◽  
Chemotherapy Agents

The circadian timing system temporally regulates biological functions relevant for psycho-physical wellbeing, spanning all the systems related to health. Hence, disruption of circadian rhythms, along with sleep cycles, is associated with the development of several diseases, including cancer. Moreover, altered circadian and sleep functions negatively impact on cancer patients’ quality of life and survival, above and beyond known determinants of outcome. This alteration can occur as a consequence of cancer, but also of anti-cancer treatments. Indeed, circadian rhythms govern also the ability of detoxifying chemotherapy agents across the 24 hours. Hence, adapting chemotherapy delivery to the molecular oscillations in relevant drug pathways can decrease toxicity to healthy cells, while increasing the number of cancer cells killing. This chronomodulated chemotherapy approach, together with the maintenance of proper circadian function throughtout the whole disease challenge, would finally result in safer and more active anticancer treatments, and in patients experiencing better quality and quantity of life.

scholarly journals Drugs of Abuse Can Entrain Circadian Rhythms

2007 ◽  
Vol 7 ◽  
pp. 203-212 ◽  
Author(s):  
Ann E. K. Kosobud ◽  
Andrea G. Gillman ◽  
Joseph K. Leffel ◽  
Norman C. Pecoraro ◽  
G. V. Rebec ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Drug Metabolism ◽  
Suprachiasmatic Nucleus ◽  
Drugs Of Abuse ◽  
Social Cues ◽  
Dark Cycle ◽  
Drug Reward ◽  
Locomotor Stimulation ◽  
Almost All

Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.

scholarly journals Maternal circadian rhythms and the programming of adult health and disease

2018 ◽  
Vol 314 (2) ◽  
pp. R231-R241 ◽  
Author(s):  
Tamara J. Varcoe ◽  
Kathryn L. Gatford ◽  
David J. Kennaway
Keyword(s):  
Circadian Rhythms ◽  
Well Being ◽  
International Travel ◽  
Adult Health ◽  
Circadian Timing ◽  
Timing System ◽  
Circadian Timing System ◽  
Delayed Sleep Phase Disorder ◽  
Delayed Sleep Phase ◽  
The Impact

The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates, and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability, and other environmental factors change predictably and repeatedly every 24 h. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias, and circadian rhythm disorders (e.g., advanced/delayed sleep phase disorder), with a growing consensus that this chronodisruption can have deleterious consequences for an individual’s health and well-being. However, the impact of chronodisruption during pregnancy on the health of both the mother and fetus is not well understood. In this review, we outline circadian timing system ontogeny in mammals and examine emerging research from animal models demonstrating long-term negative implications for progeny health following maternal chronodisruption during pregnancy.

Circadian rhythms of temperature and activity in obese and lean Zucker rats

1995 ◽  
Vol 269 (5) ◽  
pp. R1038-R1043 ◽  
Author(s):  
D. M. Murakami ◽  
B. A. Horwitz ◽  
C. A. Fuller
Keyword(s):  
Circadian Rhythms ◽  
Female Rats ◽  
Zucker Rats ◽  
Circadian Regulation ◽  
Circadian Timing ◽  
Lighting Conditions ◽  
Timing System ◽  
Circadian Timing System ◽  
Obese Zucker Rats ◽  
Normal Light

The circadian timing system is important in the regulation of feeding and metabolism, both of which are aberrant in the obese Zucker rat. This study tested the hypothesis that these abnormalities involve a deficit in circadian regulation by examining the circadian rhythms of body temperature and activity in lean and obese Zucker rats exposed to normal light-dark cycles, constant light, and constant dark. Significant deficits in both daily mean and circadian amplitude of temperature and activity were found in obese Zucker female rats relative to lean controls in all lighting conditions. However, the circadian period of obese Zucker rats did not exhibit differences relative to lean controls in either of the constant lighting conditions. These results indicate that although the circadian regulation of temperature and activity in obese Zucker female rats is in fact depressed, obese rats do exhibit normal entrainment and pacemaker functions in the circadian timing system. The results suggest a deficit in the process that generates the amplitude of the circadian rhythm.

Environmental synchronizers of squirrel monkey circadian rhythms

1977 ◽  
Vol 43 (5) ◽  
pp. 795-800 ◽  
Author(s):  
F. M. Sulzman ◽  
C. A. Fuller ◽  
M. C. Moore-Ede
Keyword(s):  
Circadian Rhythms ◽  
Squirrel Monkey ◽  
Water Availability ◽  
The Other ◽  
Saimiri Sciureus ◽  
Cool Temperature ◽  
Timing System ◽  
Circadian Timing System ◽  
Free Running ◽  
Phase Relationships

Various temporal signals in the environment were tested to determine if they could synchronize the circadian timing system of the squirrel monkey (Saimiri sciureus). The influence of cycles of light and dark, eating and fasting, water availability and deprivation, warm and cool temperature, sound and quiet, and social interaction and isolation was examined on the drinking and activity rhythms of unrestrained monkeys. In the absence of other time cues, 24-h cycles of each of these potential synchronizers were applied for up to 3 wk, and the periods of the monkey's circadian rhythms were examined. Only light-dark cycles and cycles of food availability were shown to be entraining agents, since they were effective in determining the period and phase of rhythmic variables. In the presence of each of the other environmental cycles, the monkey's circadian rhythms exhibited free-running periods which were significantly different from 24 h with all possible phase relationships between the rhythms and the environmental cycles being examined.

scholarly journals KLF10 integrates circadian timing and sugar signaling to coordinate hepatic metabolism

2020 ◽  
Author(s):  
Anthony A. Ruberto ◽  
Aline Gréchez-Cassiau ◽  
Sophie Guérin ◽  
Luc Martin ◽  
Johana S. Revel ◽  
...  
Keyword(s):  
Target Genes ◽  
Sugar Metabolism ◽  
Hepatic Metabolism ◽  
Central Carbon Metabolism ◽  
Circadian Timing ◽  
Circadian Expression ◽  
Timing System ◽  
Circadian Timing System ◽  
Negative Health Outcomes ◽  
Sugar Beverage

AbstractThe mammalian circadian timing system and metabolism are highly interconnected, and disruption of this coupling is associated with negative health outcomes. Krüppel-like factors (KLFs) are transcription factors that govern metabolic homeostasis in various organs. Many KLFs show a circadian expression in the liver. Here, we show that the loss of the clock-controlled KLF10 in hepatocytes results in extensive reprogramming of the mouse liver circadian transcriptome, which in turn, alters the temporal coordination of pathways associated with energy metabolism. We also show that glucose and fructose induce Klf10, which helps mitigate glucose intolerance and hepatic steatosis in mice challenged with a sugar beverage. Functional genomics further reveal that KLF10 target genes are primarily involved in central carbon metabolism. Together, these findings show that in the liver, KLF10 integrates circadian timing and sugar metabolism related signaling, and serves as a transcriptional brake that protects against the deleterious effects of increased sugar consumption.

scholarly journals Evidence that pain sensitivity is rhythmic in humans, mainly driven by the endogenous circadian system and little by sleep

2020 ◽  
Author(s):  
I Daguet ◽  
V Raverot ◽  
D Bouhassira ◽  
C Gronfier
Keyword(s):  
Pain Management ◽  
Pain Sensitivity ◽  
Time Of Day ◽  
Circadian System ◽  
Circadian Timing ◽  
Healthy Humans ◽  
Wide Range ◽  
Timing System ◽  
Circadian Timing System ◽  
Sensitivity To Pain

AbstractPain intensity has been reported to fluctuate during the day in some experimental and clinical conditions, but the mechanisms underlying these fluctuations are unknown. Although the circadian timing system is known to regulate a wide range of physiological functions, its implication in pain regulation is unknown. We show here, using highly controlled laboratory constant routine conditions, that pain sensitivity is rhythmic over the 24-hours and strongly controlled by the endogenous circadian timing system. We find that pain sensitivity follows a sinusoidal circadian rhythmicity, with a maximum in the middle of the night and a minimum in the afternoon. We also find a weak homeostatic control of pain sensitivity, with a linear increase over the 34 hours of prolonged wakefulness, which parallels that of sleep pressure. Using mathematical modelling, we describe that the circadian system accounts for 80% of the full magnitude of pain sensitivity over the 24 hours, and that sleep-related processes account for only 20%. This result reveals that nocturnal analgesia is predominantly induced by the circadian system and has been wrongly attributed only to sleep. Our findings highlight the need to consider the time of day in pain assessment, and suggest that personalized circadian medicine may be a promising approach to pain management.Significance statementWe discovered that sensitivity to pain is rhythmic in healthy humans, that sensitivity is maximal at night and minimal in the afternoon. Contrarily to the current thinking that sleep is the best painkiller, we find that the 24-h rhythmicity of sensitivity to pain is mainly controlled by a biological circadian clock in our body, and very little by our sleep. Our article reveals the neurobiological mechanisms involved in driving the rhythmicity of pain perception in humans, with the main time-piece located in the brain (the suprachiasmatic nuclei in the hypothalamus). Our findings challenge the current vision of pain physiology, and reveal the need to consider time-of-day and internal biological time for pain evaluation and pain management.

scholarly journals Circadian rhythms and reproduction

Reproduction ◽  
2006 ◽  
Vol 132 (3) ◽  
pp. 379-392 ◽  
Author(s):  
Michael J Boden ◽  
David J Kennaway
Keyword(s):  
Circadian Rhythms ◽  
Reproductive Performance ◽  
Clock Genes ◽  
Strain Differences ◽  
Reproductive Function ◽  
Circadian Timing ◽  
Wide Range ◽  
Timing System ◽  
Circadian Timing System

There is a growing recognition that the circadian timing system, in particular recently discovered clock genes, plays a major role in a wide range of physiological systems. Microarray studies, for example, have shown that the expression of hundreds of genes changes many fold in the suprachiasmatic nucleus, liver heart and kidney. In this review, we discuss the role of circadian rhythmicity in the control of reproductive function in animals and humans. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance, but there are sufficient redundancies in their function that many of the knockout mice produced do not show overt reproductive failure. Furthermore, important strain differences have emerged from the studies especially between the variousClock(CircadianLocomotorOutputCycleKaput) mutant strains. Nevertheless, there is emerging evidence that the primary clock genes,ClockandBmal1(Brain andMuscleARNT-like protein 1, also known asMop3), strongly influence reproductive competency. The extent to which the circadian timing system affects human reproductive performance is not known, in part, because many of the appropriate studies have not been done. With the role ofClockandBmal1in fertility becoming clearer, it may be time to pursue the effect of polymorphisms in these genes in relation to the various types of infertility in humans.

scholarly journals KLF10 integrates circadian timing and sugar signaling to coordinate hepatic metabolism

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anthony A Ruberto ◽  
Aline Gréchez-Cassiau ◽  
Sophie Guérin ◽  
Luc Martin ◽  
Johana S Revel ◽  
...  
Keyword(s):  
Target Genes ◽  
Sugar Metabolism ◽  
Hepatic Metabolism ◽  
Central Carbon Metabolism ◽  
Circadian Timing ◽  
Circadian Expression ◽  
Timing System ◽  
Circadian Timing System ◽  
Negative Health Outcomes ◽  
Sugar Beverage

The mammalian circadian timing system and metabolism are highly interconnected, and disruption of this coupling is associated with negative health outcomes. Krüppel-like factors (KLFs) are transcription factors that govern metabolic homeostasis in various organs. Many KLFs show a circadian expression in the liver. Here, we show that the loss of the clock-controlled KLF10 in hepatocytes results in extensive reprogramming of the mouse liver circadian transcriptome, which in turn, alters the temporal coordination of pathways associated with energy metabolism. We also show that glucose and fructose induce Klf10, which helps mitigate glucose intolerance and hepatic steatosis in mice challenged with a sugar beverage. Functional genomics further reveal that KLF10 target genes are primarily involved in central carbon metabolism. Together, these findings show that in the liver, KLF10 integrates circadian timing and sugar metabolism related signaling, and serves as a transcriptional brake that protects against the deleterious effects of increased sugar consumption.

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