Caffeine Alters Diurnal Variation in Ethanol-Induced Ataxia in Mice

Ruby, Christina L.; Marinos, Laura N.; Zisk, Catherine F.; Zhang, Jiawen; Palmer, Kaitlyn N.; Bunion, David J; Dietzel, Jacob D; Verbanes, Natalie M.

doi:10.4172/2329-6488.1000246

Cited by 2 publications

(2 citation statements)

References 35 publications

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“…However, as many of the age-dependent behavioral changes discussed above, including alcohol drinking, ethanol-induced loss of righting reflex (LORR) and ataxia, and memory functions vary diurnally and are regulated in part by the circadian clock (Perreau-Lenz et al, 2009, Ruby et al, 2013, Ruby et al, 2008, Ruby et al, 2016), there is a clear need to understand the role of the circadian system in alcohol-related behavior during adolescence. To begin addressing this gap in our knowledge, we compared the effect of acute ethanol on photic phase-resetting, the primary mechanism by which circadian rhythms are synchronized to the environment, in adolescent and adult mice.…”

Section: Introductionmentioning

confidence: 99%

Differential Sensitivity to Ethanol‐Induced Circadian Rhythm Disruption in Adolescent and Adult Mice

Ruby

Palmer

Zhang

et al. 2016

Alcoholism Clin & Exp Res

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Background 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 (SCN), a biological clock whose timing is synchronized (reset) to the environment primarily by light (photic) input. Alcohol (ethanol) 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 ethanol has similar effects on circadian regulation during adolescence. Methods General circadian locomotor activity was monitored in male C57BL6/J mice beginning in adolescence (P27) or adulthood (P61) in a 12 h light, 12 h dark photocycle for ~2 weeks to establish baseline circadian activity measures. On the day of the experiment, mice received an acute injection of ethanol (1.5 g/kg, i.p.) or equal volume saline 15 min prior to a 30-min light pulse at Zeitgeber Time 14 (2 h into the dark phase), 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. Results While adults showed the expected decrease in photic phase-delays induced by acute ethanol, 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. Conclusions Collectively, our results indicate that adolescent mice are less sensitive to the effect of ethanol on circadian photic phase-resetting and that their daily activity rhythms are markedly different than those of adults.

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Section: Introductionmentioning

confidence: 99%

Differential Sensitivity to Ethanol‐Induced Circadian Rhythm Disruption in Adolescent and Adult Mice

Ruby

Palmer

Zhang

et al. 2016

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

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“…In line with this idea, adolescent rodents and humans are markedly less sensitive than adults to other aversive effects of ethanol, including ataxia and sedation, and they retain these phenotypes into adulthood after AIE (Spear, 2018; White et al, 2002). Sensitivity to ethanol-induced ataxia and sedation vary diurnally in adult mice, both with a nadir at the beginning of rest phase (Perreau-Lenz et al, 2009, Ruby et al, 2016); rhythmicity in ethanol-induced sedation is absent in mice lacking the circadian clock gene mPer2 (Perreau-Lenz et al, 2009). In humans, the stimulatory (rewarding) effects of alcohol appear to be governed by the circadian clock, peaking in the early evening when drinking is also most likely to occur (Van Reen et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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

Ruby

Paye

Fabi

et al. 2018

Alcoholism Clin & Exp Res

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Background: Evidence supports a role for the circadian system in alcohol use disorders, but the impact of adolescent alcohol exposure on circadian timing later in life is unknown. Acute ethanol attenuates circadian photic phase-resetting in adult, but not adolescent, rodents. However, nearly all studies have focused on males and it is unknown whether this adolescent-typical insensitivity to ethanol persists into adulthood after adolescent drinking. Methods: Circadian activity was monitored in C57BL6/J mice receiving adolescent intermittent ethanol (AIE) exposure (15% ethanol and water every other day throughout adolescence) or water alone followed by 24 days wherein ethanol was not available (washout). Mice then received a challenge dose of ethanol (1.5 g/kg, i.p.) or saline 15 min prior to a 30-min phase-delaying light pulse, then were released into constant darkness (DD). To control for possible phase-shifting by ethanol challenge alone, a separate group of mice underwent AIE exposure (or water-only) and washout, then received an ethanol or saline injection, but did not receive a light pulse prior to DD. Results: Striking sex differences in nearly all measures of circadian photic entrainment were observed during adolescence but AIE effects were subtle and few. Only ethanol-naïve adult male mice showed attenuated photic phase-shifts with ethanol challenge, while all other groups showed normal phase-resetting responses to light. AIE-exposed females showed a persistent delay in activity offset. Conclusions: Adult male AIE-exposed mice retained adolescent-like insensitivity to ethanol-induced suppression of photic phase-resetting, suggesting AIE-induced ‘lock-in’ of an adolescent behavioral phenotype. Adult AIE-exposed females showed delayed initiation of the rest phase. Our results also indicate that intermittent ethanol drinking has subtle effects on circadian activity in mice during adolescence that differ from previously reported effects on adult males. The observed sex differences in circadian activity, ethanol consumption and preference, and responses to ethanol challenge merit future mechanistic study.

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Caffeine Alters Diurnal Variation in Ethanol-Induced Ataxia in Mice

Cited by 2 publications

References 35 publications

Differential Sensitivity to Ethanol‐Induced Circadian Rhythm Disruption in Adolescent and Adult Mice

Differential Sensitivity to Ethanol‐Induced Circadian Rhythm Disruption in Adolescent and Adult Mice

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

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