Voluntary Binge Consumption of Ethanol in a Sweetened, Chocolate-Flavored Solution by Male and Female Adolescent Sprague Dawley Rats.

BACKGROUND: The still maturing adolescent brain may be particularly vulnerable to lasting consequences of ethanol (EtOH) exposure. Yet, human adolescents are the age group most likely to engage in binge drinking (a pattern of drinking leading to blood EtOH concentrations (BECs) of 80 mg/dl or greater). Most studies to date assessing the long-term effects of adolescent EtOH exposure in outbred rodent populations have either used experimenter-administered EtOH to produce BECs in the binge range or assessed voluntary intake of EtOH at well below binge levels. Beginning with a modified schedule-induced polydipsia (SIP) procedure, this study examined the suitability of several approaches to induce voluntary binge-like consumption during adolescence in an outbred rat strain. METHODS: Adolescent male and female Sprague Dawley rats were food deprived to 85% projected free-feeding weights beginning on postnatal day (P) 24 and were given 30 minutes of access to 10% EtOH in chocolate Boost® or Boost® alone daily from P28 to P41 (followed later by their daily allocation of food). Animals were tested within operant chambers (Exp. 1a, 1b and Exp. 2) or home and novel cages (Exp. 3). Animals received either scheduled delivery of banana pellets to examine SIP (Exp. 1a,b) or massed pellet presentation (Exp. 2 and Exp. 3). Blood samples were collected via the lateral tail vein on P33 and P41. RESULTS: Intakes produced BECs frequently in the binge range (>80 mg/dl) and modeled binge-like consumption patterns, with high consumption days typically followed by 1 to 2 days of lower consumption; this variability was less evident with Boost® alone. Consumption was not schedule induced and was generally high across all studies, although consumption in males appeared to be particularly pronounced when animals were tested in the presence of their cage mate. CONCLUSIONS: Binge-like patterns of EtOH consumption were produced using these procedures in adolescent Sprague Dawley rats of both sexes and may prove to be a useful model for work examining the short- and long-term consequences of high levels of voluntary EtOH intake in adolescence.

Effects of chronic intermittent ethanol exposure during early and late adolescence on anxiety-like behaviors and behavioral flexibility in adulthood.

Although both humans and laboratory rodents demonstrate cognitive and affective alterations associated with adolescent alcohol exposure, it is still unknown whether the consequences of early initiation of alcohol use differ from those of later binge drinking within the adolescent developmental period. The present study was designed to assess the effects of early and late AIE on (1) anxiety-like behavior under social (modified social interaction test) and non-social test circumstances (modified light/dark box test, elevated plus maze), and (2) behavioral flexibility, indexed via set shifting in males and females. Early-mid adolescent intermittent exposure (early AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (late AIE) was conducted between P45 and P65, with behavioral testing initiated not earlier than 25 days after repeated exposure to ethanol (4.0 g/kg intragastrically, every other day for a total of 11 exposures). Anxiety-like behavior on the EPM was evident in males and females following early AIE, whereas only males demonstrated non-social anxiety on the EPM following late AIE. Social anxiety-like alterations and deficits in behavioral flexibility were evident only in males following early AIE. Taken together, the results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol and an insensitivity of older adolescent females to the intermittent ethanol exposure paradigm.

Voluntary elevated ethanol consumption in adolescent Sprague-Dawley rats: Procedural contributors and age-specificity.

Alcohol consumption is typically initiated during adolescence, with the incidence of binge drinking (production of blood ethanol concentrations [BECs] > 80 mg/dL) peaking during this stage of development. Studies in outbred rats investigating the consequences of adolescent ethanol exposure have typically employed intragastric, vapor, or intraperitoneal administration to attain BECs in this range. While these procedures have yielded valuable data regarding the consequences of adolescent exposure, they are varyingly stressful, administer the full dose at once, and/or bypass digestion. Consequently, we have worked to develop a model of voluntary elevated ethanol consumption in outbred adolescent Sprague-Dawley males and females, building on our previous work (see Hosová & Spear, 2017). This model utilizes daily 30-min access to 10% ethanol (v/v) in chocolate Boost® from postnatal day (P)28-41. Experiment 1 compared intake levels between (1a) animals given either ball-bearing or open-ended sipper tube tips for solution access, (1b) animals separated from their cage mate by wire mesh or isolated to a separate cage during solution access, (1c) animals given solution access with or without simultaneous access to banana-flavored sugar pellets, and (1d) animals that were either moderately food-restricted or fed ad libitum. Experiment 2 compared intake levels between animals given daily solution access and animals given access only on a "Monday-Wednesday-Friday" intermittent schedule. Experiment 3 compared adolescent and adult (P70-83) consumption using the finalized procedure as based on the results of Experiments 1 and 2. As in our previous work, consumptions well within the binge range were produced on some days, with high-consumption days typically followed by several days of lower consumption before increasing again. Sipper tube type (1a) and simultaneous pellet access (1c) did not affect consumption, while intake was significantly higher in non-isolated (1b), food-restricted (1d), daily-access (2), and adolescent (3) animals. However, although ethanol intake was higher in food-restricted animals, the resulting BECs were equivalent or higher in non-restricted animals, likely due to a hepatoprotective effect of moderate food restriction. Post-consumption intoxication ratings correlated with BECs and were notably higher in adults than adolescents, despite the lower voluntary consumption levels of adults, confirming prior reports of the attenuated sensitivity of adolescents to ethanol intoxication relative to adults. The final model utilized ball-bearing sipper tube tips to provide daily access to 10% ethanol in chocolate Boost® to free-feeding adolescent animals separated from their cage mate by wire mesh, with no food provided during solution access. This easy-to-implement model is effective in producing elevated voluntary ethanol consumption in adolescent, but not adult, Sprague-Dawley rats.