title: Differential Sensitivity to Ethanol-Induced Circadian Rhythm Disruption in Adolescent and Adult Mice.
abstract: Growing evidence supports a central role for the circadian system in alcohol use disorders, but few studies have examined this relationship during adolescence. In mammals, circadian rhythms are regulated by the suprachiasmatic nucleus, a biological clock whose timing is synchronized (reset) to the environment primarily by light (photic) input. Alcohol (ethanol [EtOH]) disrupts circadian timing in part by attenuating photic phase-resetting responses in adult rodents. However, circadian rhythms change throughout life and it is not yet known whether EtOH has similar effects on circadian regulation during adolescence.
  
  
  
  General circadian locomotor activity was monitored in male C57BL6/J mice beginning in adolescence (P27) or adulthood (P61) in a 12-hour light, 12-hour dark photocycle for ~2 weeks to establish baseline circadian activity measures. On the day of the experiment, mice received an acute injection of EtOH (1.5 g/kg, i.p.) or equal volume saline 15 minutes prior to a 30-minute light pulse at Zeitgeber Time 14 (2 hours into the dark phase) and then were released into constant darkness (DD) for ~2 weeks to assess phase-resetting responses. Control mice of each age-group received injections but no light pulse prior to DD.
  
  
  
  While adults showed the expected decrease in photic phase-delays induced by acute EtOH, this effect was absent in adolescent mice. Adolescents also showed baseline differences in circadian rhythmicity compared to adults, including advanced photocycle entrainment, larger photic phase-delays, a shorter free-running (endogenous) circadian period, and greater circadian rhythm amplitude.
  
  
  
  Collectively, our results indicate that adolescent mice are less sensitive to the effect of EtOH on circadian photic phase-resetting and that their daily activity rhythms are markedly different than those of adults.
authors.affiliation: Department of Biology, Indiana University of Pennsylvania, Indiana, Pennsylvania.
authors.forename: Christina L
authors.identifier: 0000-0002-4218-7286
authors.initials: CL
authors.lastname: Ruby
authors.affiliation: Department of Biology, Indiana University of Pennsylvania, Indiana, Pennsylvania.
authors.forename: Kaitlyn N
authors.initials: KN
authors.lastname: Palmer
authors.affiliation: Department of Biology, Indiana University of Pennsylvania, Indiana, Pennsylvania.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biology, Indiana University of Pennsylvania, Indiana, Pennsylvania.
authors.forename: Megan O
authors.initials: MO
authors.lastname: Risinger
authors.affiliation: Department of Biology, Indiana University of Pennsylvania, Indiana, Pennsylvania.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Butkowski
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina.|Neurobiology Research Laboratory, VA Medical Center, Durham, North Carolina.
authors.forename: H Scott
authors.initials: HS
authors.lastname: Swartzwelder
mesh_terms: D000367:Age Factors; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010775:Photic Stimulation / Q000379:methods*
chemical_list: D000431:Ethanol
keywords: Adolescent; Alcohol; Circadian; Photic Phase-Resetting