Time course of elevated ethanol intake in adolescent relative to adult rats under continuous, voluntary-access conditions.

The Transition through adolescence is a unique developmental period. It is characterized by numerous behavioral, hormonal, and neural changes in humans as well as nonhuman mammals (see Spear, 2000 for a review). Among the behaviors characteristic of both human adolescents (Arnett, 1992; Maggs et al., 1995) as well as adolescent rodents (Primus and Kellogg, 1989; Spear et al., 1980; Vanderschuren et al., 1997) are increases in risk-taking and peer-directed social interactions. Drug and alcohol experimentation also becomes common among human adolescents during this time. The prevalence of alcohol use and misuse is surprisingly high in this age group, with 80% of 12th graders reporting having tried alcohol at least once and almost 30% of them reporting binge consumption within the past 2 weeks (Johnston et al., 2001). This high rate of alcohol use may have implications for development of later alcohol use disorders. Although causality cannot be inferred from these data, the results from the National Longitudinal Alcohol Epidemiological Survey found that initiation of alcohol use before the age of 14 increased the rate of lifetime alcohol dependency to 40%, whereas the rate was only 10% in those initiating use after the age of 20 (Grant and Dawson, 1997). As ethical constraints limit investigation of factors that contribute to elevated alcohol consumption during adolescence in humans, animal models of ethanol (EtOH) intake during adolescence are of importance. In a rat model, postnatal days (P)28 to 42 have been conservatively defined as prototypic adolescence based on characteristic neurobehavioral changes, with some signs of adolescence persisting in male adolescents until P55 to 60 (Spear, 2000). This time period itself may not be homogeneous, and can be further subdivided functionally into early, mid, and late phases (see Adriani et al., 2002; Varlinskaya and Spear, 2004, 2006a). Support for distinct subphases within the broader adolescent period includes the literature describing differential behavioral sensitivity to ethanol and other drugs of abuse during early versus late adolescence (see Adriani et al., 2002; Belluzzi et al., 2004; Silveri and Spear, 1998; Varlinskaya and Spear, 2006a). For instance, when examining hypnotic effects following challenge with a high dose of ethanol, early adolescent Sprague–Dawley rats were found to recover more rapidly from ethanol-induced sedation than late adolescent animals (Silveri and Spear, 1998). Similarly, early adolescent Sprague–Dawley rats (P28) were found to be more sensitive to ethanol-induced social facilitation in a familiar environment and less sensitive to the anxiolytic effects of ethanol in an unfamiliar environment than their late adolescent (P42) counterparts (Varlinskaya and Spear, 2006a). Although few studies using animal models have compared voluntary ethanol intake in adolescents and adults, several of the available studies have reported that elevated ethanol consumption is not limited to human adolescents (Doremus et al., 2005; Lancaster et al., 1996). In other studies, however, relatively moderate levels of voluntary ethanol intake have been reported in adolescent Long–Evans rats (Honey and Galef, 2003; Siciliano and Smith, 2001), although these studies were not designed to directly compare adolescent ethanol consumption with that of adults. Methodological differences across experiments may contribute to the mixed results observed in the literature. Previous research within our laboratory (Doremus et al., 2005) has repeatedly found that adolescent Sprague–Dawley rats voluntarily consume more ethanol than adults on a gram per kilogram basis, with adolescent intake tending to decline over the course of the 1 to 2-week assessment period while remaining significantly higher than that of adults. However, various environmental and procedural variables have been shown to exert notable influences on this intake (Doremus et al., 2005). For instance, in a home cage, 2-bottle choice paradigm, ethanol intake of adolescents was found to be insensitive to the intake-suppressing effect of single housing seen in adults, with adolescent animals drinking similar amounts of ethanol regardless of experimental housing condition (Doremus et al., 2005). Similarly, in a study examining postweaning housing conditions and initiation of ethanol-drinking procedure, McKinzie et al. (1998) found that neither postweaning housing condition nor initiation procedure affected levels of ethanol consumption in periadolescent alcohol-preferring (P) rats. In contrast, ethanol intake among adolescent, but not adult Sprague–Dawley rats, was found to be exacerbated when the solution was presented in ball-bearing–containing ball-point (BP) sipper tubes rather than open-ended tubes, with adolescents drinking from BP tubes developing a preference for ethanol over water (Doremus et al., 2005). Elevated ethanol intake among adolescents was also shown in this study not to be due to the inherent high caloric value of the ethanol solution. Despite evidence that early alcohol exposure is correlated with later alcohol dependency and alcohol use disorders in humans (Dewit et al., 2000; Grant and Dawson, 1997), there have been relatively few studies in laboratory animals examining the impact of chronic adolescent ethanol exposure on later consumption in adulthood in outbred animals. Studies looking at ethanol exposure during adolescence and later ethanol drinking in adulthood have found mixed results. Male periadolescent BALB/cByJ mice given a 2-bottle choice access to ethanol were found to have increased ethanol preference in adulthood (Blizard et al., 2004). Studies examining free-choice ethanol exposure during adolescence and later operant self-administration of ethanol in adulthood in P rats have found that P rats exposed during adolescence learned to self-administer ethanol more rapidly in adulthood and displayed more ethanol-seeking behavior as adults than naive P rats (Rodd-Henricks et al., 2002a). In a companion study, adult P rats given free-choice pre-exposure beginning in adulthood and later tested after a comparable amount of time did not show increased ethanol seeking in an operant paradigm (Rodd-Henricks et al., 2002b). In another study comparing 24-hour drinking patterns of adolescent and adult P rats over a 4-week period, adolescent male rats were found to exhibit more of an increase in ethanol licking behavior across weeks than adult males (Bell et al., 2006). High-alcohol–drinking rats (HAD) given 2-bottle choice access to ethanol solutions and water throughout adolescence and early adulthood (P30–60) also showed increased consumption (g/kg/d) and preference for ethanol over time (Bell et al., 2004). However, forced administration via ethanol vapor or forced consumption during adolescence did not result in increased intake in adult Sprague–Dawley rats (Slawecki and Betancourt, 2002; Tolliver and Samson, 1991). Most of these studies exposing animals to ethanol during adolescence assessed ethanol-drinking behavior in adulthood after a period of abstinence in postadolescence or early adulthood and did not include an adult comparison group or, alternatively, were conducted in animals bred to prefer alcohol. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake seen in adolescent animals and during the adolescent-to-adult transition in outbred animals using a continuous access, 2-bottle choice paradigm, and to contrast this intake with ontogenetic patterns of food and water intake. By comparing intake in adulthood of animals initially given access to ethanol in adolescence with those whose initial experiences with ethanol began in adulthood, these studies were also designed to determine whether extended home cage access to ethanol during adolescence elevates subsequent rates of voluntary ethanol drinking in adulthood.