title: Acute ethanol disrupts photic and serotonergic circadian clock phase-resetting in the mouse.
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.
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, OH 44242, USA.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Brager
authors.forename: Christina L
authors.initials: CL
authors.lastname: Ruby
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Prosser
authors.forename: J David
authors.initials: JD
authors.lastname: Glass
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D057906:Circadian Clocks / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects*; D035061:Control Groups; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D010775:Photic Stimulation; D017440:Photoperiod; D011985:Receptors, Serotonin / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D000431:Ethanol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin