» Articles » PMID: 21463340

Acute Ethanol Disrupts Photic and Serotonergic Circadian Clock Phase-resetting in the Mouse

Overview
Specialty Psychiatry
Date 2011 Apr 6
PMID 21463340
Citations 23
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Alcohol dependence is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol dependence on the circadian timing system. In this study, we extend previous work in C57BL/6J mice to: (i) characterize the suprachiasmatic nucleus (SCN) pharmacokinetics of acute systemic ethanol administration, (ii) explore the effects of acute ethanol on photic and nonphotic phase-resetting, and (iii) determine if the SCN is a direct target for photic effects.

Methods: First, microdialysis was used to characterize the pharmacokinetics of acute intraperitoneal (i.p.) injections of 3 doses of ethanol (0.5, 1.0, and 2.0 g/kg) in the mouse SCN circadian clock. Second, the effects of acute i.p. ethanol administration on photic phase delays and serotonergic ([+]8-OH-DPAT-induced) phase advances of the circadian activity rhythm were assessed. Third, the effects of reverse-microdialysis ethanol perfusion of the SCN on photic phase-resetting were characterized.

Results: Peak ethanol levels from the 3 doses of ethanol in the SCN occurred within 20 to 40 minutes postinjection with half-lives for clearance ranging from 0.6 to 1.8 hours. Systemic ethanol treatment dose-dependently attenuated photic and serotonergic phase-resetting. This treatment also did not affect basal SCN neuronal activity as assessed by Fos expression. Intra-SCN perfusion with ethanol markedly reduced photic phase delays.

Conclusions: These results confirm that acute ethanol attenuates photic phase-delay shifts and serotonergic phase-advance shifts in the mouse. This dual effect could disrupt photic and nonphotic entrainment mechanisms governing circadian clock timing. It is also significant that the SCN clock is a direct target for disruptive effects of ethanol on photic shifting. Such actions by ethanol could underlie the disruptive effects of alcohol abuse on behavioral, physiological, and endocrine rhythms associated with alcoholism.

Citing Articles

Sleep-Related Predictors of Risk for Alcohol Use and Related Problems in Adolescents and Young Adults.

Hasler B, Schulz C, Pedersen S Alcohol Res. 2024; 44(1):02.

PMID: 38500552 PMC: 10948113. DOI: 10.35946/arcr.v44.1.02.


Human circadian rhythm studies: Practical guidelines for inclusion/exclusion criteria and protocol.

Yousefzadehfard Y, Wechsler B, DeLorenzo C Neurobiol Sleep Circadian Rhythms. 2022; 13:100080.

PMID: 35989718 PMC: 9382328. DOI: 10.1016/j.nbscr.2022.100080.


Sex Differences in Photic Entrainment and Sensitivity to Ethanol-Induced Chronodisruption in Adult Mice After Adolescent Intermittent Ethanol Exposure.

Ruby C, Paye G, Fabi J, Zhang J, Risinger M, Palmer K Alcohol Clin Exp Res. 2018; 42(11):2144-2159.

PMID: 30102762 PMC: 6214762. DOI: 10.1111/acer.13867.


: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse.

De Nobrega A, Lyons L Neural Plast. 2018; 2017:4723836.

PMID: 29391952 PMC: 5748135. DOI: 10.1155/2017/4723836.


Circadian Rhythms and Substance Abuse: Chronobiological Considerations for the Treatment of Addiction.

Webb I Curr Psychiatry Rep. 2017; 19(2):12.

PMID: 28188587 DOI: 10.1007/s11920-017-0764-z.


References
1.
Challet E, Scarbrough K, PENEV P, Turek F . Roles of suprachiasmatic nuclei and intergeniculate leaflets in mediating the phase-shifting effects of a serotonergic agonist and their photic modulation during subjective day. J Biol Rhythms. 1998; 13(5):410-21. DOI: 10.1177/074873098129000237. View

2.
Prosser R . Serotonin phase-shifts the mouse suprachiasmatic circadian clock in vitro. Brain Res. 2003; 966(1):110-5. DOI: 10.1016/s0006-8993(02)04206-3. View

3.
Horikawa K, Shibata S . Phase-resetting response to (+)8-OH-DPAT, a serotonin 1A/7 receptor agonist, in the mouse in vivo. Neurosci Lett. 2004; 368(2):130-4. DOI: 10.1016/j.neulet.2004.06.072. View

4.
Prosser R, Mangrum C, Glass J . Acute ethanol modulates glutamatergic and serotonergic phase shifts of the mouse circadian clock in vitro. Neuroscience. 2008; 152(3):837-48. PMC: 2377014. DOI: 10.1016/j.neuroscience.2007.12.049. View

5.
Smart R . Drinking problems among employed, unemployed and shift workers. J Occup Med. 1979; 21(11):731-6. DOI: 10.1097/00043764-197911000-00005. View