Chronic ethanol consumption impairs the circadian rhythm of pro‐opiomelanocortin and period genes mRNA expression in the hypothalamus of the male rat

Chen, Cui Ping; Kühn, Peter; Advis, J. P.; Sarkar, Dipak K.

doi:10.1046/j.1471-4159.2003.02300.x

Cited by 113 publications

(92 citation statements)

References 62 publications

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“…Although we did not measure Clock expression in the SCN, others have shown that the SCN is responsive to ethanol (Chen et al, 2004;Prosser and Glass, 2009;. Studies in different species have illustrated that circadian clock neurons are important for alcohol tolerance and that alcohol can modulate circadian phase-shifting (Brager et al, 2010;Ghezzi et al, 2013;McElroy et al, 2009;Prosser and Glass, 2009;Ruby et al, 2009;.…”

Section: Discussionmentioning

confidence: 88%

“…In addition, studies have reported in rodents that chronic consumption of high levels of ethanol can alter rPer2 gene expression in the SCN and activity rhythms (Chen et al, 2004;. Furthermore, variations (SNPs or mutations) in the Clock gene and the Per2 gene associate with increased alcohol consumption in humans (Spanagel et al, 2005b;Sjoholm et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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The Role of Clock in Ethanol-Related Behaviors

Ozburn

Falcón

Mukherjee

et al. 2013

Neuropsychopharmacol

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Mice with a mutation in the Clock gene (ClockD19) exhibit increased preference for stimulant rewards and sucrose. They also have an increase in dopaminergic activity in the ventral tegmental area (VTA) and a general increase in glutamatergic tone that might underlie these behaviors. However, it is unclear if their phenotype would extend to a very different class of drug (ethanol), and if so, whether these systems might be involved in their response. Continuous access voluntary ethanol intake was evaluated in ClockD19 mutants and wild-type (WT) mice. We found that ClockD19 mice exhibited significantly increased ethanol intake in a two-bottle choice paradigm. Interestingly, this effect was more robust in female mice. Moreover, chronic ethanol experience resulted in a long-lasting decrease in VTA Clock expression. To determine the importance of VTA Clock expression in ethanol intake, we knocked down Clock expression in the VTA of WT mice via RNA interference. We found that reducing Clock expression in the VTA resulted in significantly increased ethanol intake similar to the ClockD19 mice. Interestingly, we also discovered that ClockD19 mice exhibit significantly augmented responses to the sedative effects of ethanol and ketamine, but not pentobarbital. However, their drinking behavior was not affected by acamprosate, an FDA-approved drug for the treatment of alcoholism, suggesting that their increased glutamatergic tone might underlie the increased sensitivity to the sedative/hypnotic properties of ethanol but not the rewarding properties of ethanol. Taken together, we have identified a significant role for Clock in the VTA as a negative regulator of ethanol intake and implicate the VTA dopamine system in this response.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

The Role of Clock in Ethanol-Related Behaviors

Ozburn

Falcón

Mukherjee

et al. 2013

Neuropsychopharmacol

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“…We have previously shown the strong influence of the opioid ␤-endorphin on NK cytolytic activity (20,34). We have found recently that pro-opiomelanocortin transcript levels in the hypothalamic arcuate nucleus follow a circadian pattern that correlates with the circadian rhythm in NK activity (42). In humans, it has been shown that plasma levels of ␤-endorphin and other endogenous opioid peptides, like ␣-melanocyte-stimulating hormone, follow a circadian profile (43).…”

Section: Discussionmentioning

confidence: 99%

Circadian Rhythms of Granzyme B, Perforin, IFN-γ, and NK Cell Cytolytic Activity in the Spleen: Effects of Chronic Ethanol

Arjona

Boyadjieva

Sarkar

2004

The Journal of Immunology

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Recent studies show that alterations in the body’s biological rhythms can lead to serious pathologies, including cancer. Acute and chronic ethanol consumption impairs the immune system by causing specific defects in the cellular components of the innate immune response and by creating increased risk and susceptibility to infections and cancer. NK cells are critical for immune surveillance against infected and malignant cells. To assess whether NK cell function follows a circadian trend and to determine ethanol effects on this rhythm, we measured, over a 24-h period, mRNA and protein levels of granzyme B, perforin, and the cytokine IFN-γ, as well as NK cell activity, in the splenocytes of ad libitum-fed, pair-fed, and ethanol-fed Sprague Dawley male rats. Circadian rhythms were found in mRNA and protein levels of granzyme B, perforin, and IFN-γ. A circadian pattern was also detected in NK cell cytolytic activity. Our data further demonstrated how chronic ethanol suppressed NK cell activity by directly disrupting the circadian rhythms of granzyme B, perforin, and IFN-γ. These findings identify the circadian functions of splenic NK cells and show the vulnerability of these rhythms to chronic ethanol.

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“…On the other hand, chronic ethanol exposure has been reported to alter both neuropeptide (vasopressin, vasoactive intestinal peptide) (Madeira et al, 1997) and circadian clock gene (per1, per2, per3) (Chen et al, 2004) expression within the SCN, and while a specific role for these elements in modulating the response of the pacemaker to phase-shifting stimuli has not been as clearly established as that for GABA and glutamate receptors, such effects could certainly contribute to ethanolinduced alterations in circadian phase-shifting as well. Reciprocally, mutation of the per2 isoform of the mouse per gene alters both glutamatergic tone and voluntary ethanol intake (Spanagel et al, 2005), further highlighting the complex interactions between ethanol intake, neurotransmitter systems, and chronobiological regulation.…”

Section: Discussionmentioning

confidence: 99%

Chronic ethanol intake modulates photic and non-photic circadian phase responses in the Syrian hamster

Seggio

Logan

Rosenwasser

2007

Pharmacology Biochemistry and Behavior

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Chronic alcohol intake disrupts sleep and other circadian biological rhythms in both human alcoholics and in experimental animals. Recent studies from our laboratory indicate that these effects may be due, in part, to ethanol-induced alterations in fundamental properties of the circadian pacemaker. The present study explored the effects of chronic voluntary ethanol intake (25% v/v) on circadian phase responses to both photic and non-photic stimuli in Syrian hamsters. Hamsters were used in these experiments because they are a popular model organism in behavioral chronobiology research, and are characterized by unusually high levels of voluntary ethanol intake. Relative to controls, ethanol exposed animals showed attenuation of circadian phase responses and wheel running activity following acute administration of the benzodiazepine, triazolam, a non-photic phase-shifting stimulus. In addition, ethanol exposed animals displayed reduced phase advances, but normal phase delays, in response to brief light pulses. While the mechanisms underlying these effects remain to be elucidated, we hypothesize that ionotropic GABA and glutamate receptors may be involved, since these proteins serve as important targets for the neurobiological effects of ethanol, and are also known to be critically involved in the modulation of photic and non-photic circadian phase responses.

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Chronic ethanol consumption impairs the circadian rhythm of pro‐opiomelanocortin and period genes mRNA expression in the hypothalamus of the male rat

Cited by 113 publications

References 62 publications

The Role of Clock in Ethanol-Related Behaviors

The Role of Clock in Ethanol-Related Behaviors

Circadian Rhythms of Granzyme B, Perforin, IFN-γ, and NK Cell Cytolytic Activity in the Spleen: Effects of Chronic Ethanol

Chronic ethanol intake modulates photic and non-photic circadian phase responses in the Syrian hamster

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