Severity of alcohol withdrawal symptoms depends on developmental stage of Long–Evans rats

Abstract

To investigate alcohol dependency and the potential role of age of initial alcohol consumption, Long-Evans (LE) rats were fed an ethanol-containing liquid diet starting at postnatal (P) ages (days): P23-27 (juvenile), P35-45 (adolescent) or P65-97 (young adult). Severity of subsequent withdrawal symptoms was dependent on age when consumption began and on duration of alcohol consumption. Frequency of withdrawal seizures was highest for rats starting consumption as juveniles, intermediate for adolescents and lowest for adults. Normalized to body weight, alcohol consumption was significantly higher for adolescent and juvenile rats than for adults. SpragueDawley rats that began alcohol consumption as adolescents (P35) had a level of alcohol consumption identical to that of the adolescent LE rats but showed much lower frequency of withdrawal seizures when tested after 2, 3 and 5 weeks of alcohol consumption. Based on several indicators, the capacity of the juveniles to metabolize ethanol is equal to or exceeds that of adults. Recoveries from a single dose of ethanol (2.5g ethanol/kg body weight) were faster for juvenile LE rats than adults. The rate of decline in blood ethanol concentration was identical for juvenile and adult rats while the corrected ethanol elimination rate was higher for juveniles. The primary isozyme of alcohol dehydrogenase (ADH) in rat liver, ADH-3, had a similar Km and higher activity in liver preparations from juveniles. In conclusion, LE rats beginning alcohol consumption as juveniles or adolescents develop a severe alcohol withdrawal syndrome that may not be attributed entirely to higher levels of consumption and was not explained by any obvious deficiencies in metabolism.

Altered Pattern of Na,K-ATPase Activity and mRNA During Chronic Alcohol Consumption by Juvenile and Adolescent Rats

“…During the experimental period, rats were housed individually. An ethanol-containing diet (Leiber and DeCarli 1982) formulated by BioServ (Frenchtown, NJ) was administrated to rats as described previously (Chung et al 2008). Consistent with accepted ranges for expected developmental shifts (Spear 2000a), rats began consuming the ethanol-containing diet at one of three postnatal starting ages (days): P25 (juvenile), P45 (adolescent), or P97 (adult).…”

“…The Long-Evans (LE) line was chosen for study because of previous work characterizing the high frequency of alcohol withdrawal seizures seen when these rats began alcohol consumption as juveniles or adolescents (Chung et al 2008). These immature LE rats also showed a higher frequency of withdrawal seizures than adolescents of the more commonly studied Sprague-Dawley (SD) strain (Chung et al 2008).…”

Brain DNA damage and behavioral changes after repeated intermittent acute ethanol withdrawal by young rats

“…On all EW days, the bottles were removed from 8 a.m. to 11 a.m., and 6 h of abstinence were imposed on each animal before re-exposure of the respective meal for all animals. According to Chung et al (2008), both juvenile and adult rats show blood ethanol concentrations (BEC) equal to 0 after 260 min of ethanol withdrawal.…”

“…Human alcohol consumption often begins during adolescence and the transition from adolescence to young adulthood in rats can serve as a model for studying toxic effects of alcohol on the brain of young animals (Chung et al 2008). In the RIEA model, the behavior observed following the alcohol deprivation period is known as Balcohol deprivation effect^(ADE) (Spanagel and Holter 1999;Sanchis-Segura and Spanagel 2006;Simms et al 2008;Rosenwasser et al 2012;Villas Boas et al 2012;Tampier et al 2013).…”

“…In animals, the behavioral manifestations during ethanol withdrawal are anxiety-like, hypoactivity, convulsions, stress, and depression-like symptoms, which may also resemble the emotional or affective symptoms seen in humans (Baldwin et al 1991;Cabral et al 2006;Doremus-Fitzwater and Spear 2007). Rats beginning alcohol consumption as adolescents may develop more severe alcohol withdrawal syndrome than adults which may not be fully attributed to higher levels of consumption or to deficiencies in alcohol metabolism (Chung et al 2008).…”