Elsevier

Alcohol

Volume 48, Issue 8, December 2014, Pages 755-763
Alcohol

Effects of ethanol exposure during adolescence or in adulthood on Pavlovian conditioned approach in Sprague-Dawley rats

https://doi.org/10.1016/j.alcohol.2014.05.006Get rights and content

Abstract

Human studies have shown that adolescents who repeatedly use alcohol are more likely to be dependent on alcohol and are more likely to suffer from psychological problems later in life. There has been limited research examining how ethanol exposure in adolescence might contribute to later abuse or addiction in adulthood. The present experiment examined effects of intermittent ethanol exposure during adolescence on sign-tracking behavior in adulthood, indexed by a Pavlovian conditioned approach (PCA) task wherein an 8s lever presentation served as a cue predicting subsequent delivery of a flavored food pellet. Although no response was required for food delivery, after multiple pairings, 1 of 2 different responses often emerged during the lever presentation: goal tracking (head entries into the food trough) or sign tracking (engagement with the lever when presented). Sign tracking is thought to reflect the attribution of incentive salience to reward-paired cues and has been previously correlated with addiction-like behaviors. Following the last PCA session, blood samples were collected for analysis of post-session corticosterone levels. Sixty-two rats (n = 10–12/group) were pseudo-randomly assigned to 1 of 2 intragastric (i.g.) exposure groups (water or 4 g/kg ethanol) or a non-manipulated (NM) control group. Animals were intubated with ethanol or water every other session from postnatal session (PND) 28–48 or PND 70–90. Rats were then tested in adulthood (PND 71–79 or PND 113–122) on the PCA task. Animals exposed chronically to ethanol during adolescence exhibited significantly higher levels of sign-tracking behavior in adulthood than NM and water-treated animals, and showed higher corticosterone than NM control animals. These effects were not seen after comparable ethanol exposure in adulthood. These results suggest that adolescent alcohol exposure has long-term consequences on the expression of potential addiction-relevant behaviors in adulthood.

Introduction

Adolescence is a developmental transition characterized by increases in social interactions with peers, elevated levels of risk taking, impulsivity, and frequent initiation of alcohol and other drug use, along with other behavioral and physiological changes (Doremus-Fitzwater et al., 2012, Johnston et al., 2012). Alcohol is the most widely used drug during this time, with approximately 42% of 12th graders reporting use within the past 30 days (Johnston, O'Malley, Bachman, & Schulenberg, 2013). Further, human adolescents show higher levels of binge drinking than their adult counterparts, with levels per occasion of ethanol use in adolescence approximately 2 times higher than in adulthood (SAMHSA, 2013). Studies with animal models likewise typically report similar increases of ethanol use in adolescence (Spear, 2013, Vetter et al., 2007, Vetter-O'Hagen et al., 2009). Elevations in adolescent drinking may have long-term consequences. Adolescents diagnosed with alcohol disorders show cognitive impairments (Brown, Tapert, Tate, & Abrantes, 2000), and adolescent drinkers are more likely to develop alcohol dependence (Grant & Dawson, 1997). From these kinds of studies alone, however, it is not possible to attribute causality of effects to alcohol exposure per se, and as such, animal studies have proved useful for investigating whether repeated exposure to alcohol during adolescence induces long-lasting consequences that are evident in adulthood.

An increasing body of literature to date has investigated the impact of adolescent intermittent alcohol exposure (AIE) on adult behaviors, with some evidence emerging that AIE may have long-term repercussions. For example, cognitive deficits (Coleman et al., 2011, Pascual et al., 2007) and increased alcohol intake under certain circumstances (Broadwater and Spear, 2013, Matthews et al., 2008) have been seen in adulthood after AIE. Yet, the data are mixed with, for instance, reports of increased ethanol consumption, contrasting with other findings of decreased ethanol consumption in adulthood after AIE (Gilpin, Karanikas, & Richardson, 2012). Few of the studies to date in this emerging literature have included adult exposure groups to determine whether or not observed consequences are specific to ethanol exposure during adolescence. Those studies that have included adults generally suggest age-specificity of effects (Fleming et al., 2012, Pascual et al., 2009).

One little-investigated area to date is the impact of AIE on future addiction vulnerabilities. Among the theories of drug addiction that may provide insight into predispositions for elevated drinking is the Incentive Sensitization Theory, which postulates a dichotomy among potential processes contributing to addiction between “wanting” and “liking”, with each having different underlying neural substrates (Robinson & Berridge, 1993). “Liking” can be thought of as the hedonic value of a reward (Robinson & Berridge, 2003), and is thought to require opioid activation in the nucleus accumbens (NAc) (Kelley and Berridge, 2002, Peciña and Berridge, 2000). In contrast, “wanting” reflects motivation for a drug reward, and is more closely associated with dopamine release within the NAc (Robinson & Berridge, 2003). It is thought that during the development of addiction, “liking” of a drug may not change, whereas “wanting” of a drug may increase with the development of incentive sensitization. Further, a cue for a reward, such as an addictive substance, can be imbued with incentive salience, thereby contributing to cue-related relapse (Berridge & Robinson, 2003).

“Wanting”/incentive salience vs. hedonic “liking” has been explored in rats using Pavlovian conditioned approach (PCA). PCA is an auto-shaping procedure in which a conditioned stimulus (CS; such as a lever) is repeatedly paired with an unconditioned stimulus (US; such as a food reward). Immediate engagement with the CS when it is presented is termed sign tracking (ST), and is thought to reflect the incentive salience of the reward cue. While some animals develop ST during PCA, others will preferentially attend to the US delivery area (i.e., food trough) during CS presentation, a behavior termed goal tracking (GT). Emergence of ST is thought to reflect the motivational property of the reward, and has the potential to develop into “pathological” incentive salience (Flagel et al., 2009, Robinson and Berridge, 2003). Sign tracking has also been linked to addiction-like behaviors (Tomie, Grimes, & Pohorecky, 2008) and can be induced by drugs of abuse (Doremus-Fitzwater and Spear, 2011, Uslaner et al., 2006). Our lab has previously shown that sign tracking in the PCA task seen in adulthood is sensitive to adolescent stress exposure (Anderson & Spear, 2011).

The purpose of experiment (Exp.) 1 was to determine the effect of adolescent ethanol exposure on later sign-tracking behavior in adulthood. The purpose of Exp. 2 was to investigate whether effects observed in Exp. 1 were age-dependent by exposing adults to comparable amounts of ethanol and testing them later in adulthood. Our hypothesis was that repeated alcohol exposure in adolescence, but not adulthood, would increase later propensity for sign tracking, perhaps reflecting an increase in later addiction vulnerability via exacerbation of the incentive salience animals assign to cues predicting rewards.

Section snippets

Subjects

Male Sprague-Dawley rats reared and raised in our colony in Binghamton University were used in the present experiments. On the day after birth, postnatal day (P)1, litters were culled to 8–10 pups, with a ratio of 6 males to 4 females preferred. Pups remained with their mothers until P21, at which point animals were pair-housed with same-sex littermates. Animals were maintained in a temperature-controlled vivarium with a 12:12 h light–dark cycle (lights on at 0700), and food (Purina rat chow,

Weight gain during exposure

Weight data for ethanol or water-exposed animals were subjected to a 2 (ethanol or water-exposed) × 11 (exposure days) repeated-measures ANOVA, which revealed a trend of group [F(1,18) = 3.520, p = 0.077], along with a significant effect of day [F(10,180) = 3998.672, p < 0.0001], as all animals continued to gain weight throughout exposure. Weight data were also analyzed including the NM animals on the first and last day of exposure (P28 and P48) using a 3 (ethanol-exposed, water-exposed, or NM

Discussion

Animals exposed to ethanol during adolescence and tested in a Pavlovian conditioning paradigm beginning 3 weeks thereafter showed significantly more sign-tracking behavior than did water-exposed and NM control animals, along with significantly higher post-session CORT levels than NM animals. With goal-tracking behavior, an opposite pattern was seen, with both water-exposed and NM controls exhibiting significantly higher goal tracking than ethanol-exposed animals. In contrast, no differences

Acknowledgments

The research presented in this paper was supported by NIH grant UO1 AA019972 – NADIA Project.

References (53)

  • G. Laviola et al.

    Striatal dopamine sensitization to Damphetamine in periadolescent but not in adult rats

    Pharmacology, Biochemistry, and Behavior

    (2001)
  • D.J. Livy et al.

    Blood ethanol concentration profiles: a comparison between rats and mice

    Alcohol

    (2003)
  • A.M. Lomanowska et al.

    Inadequate early social experience increases the incentive salience of reward-related cues in adulthood

    Behavioural Brain Research

    (2011)
  • D.B. Matthews et al.

    Chronic intermittent exposure to ethanol during adolescence produces tolerance to the hypnotic effects of ethanol in male rats: a dose-dependent analysis

    Alcohol

    (2008)
  • S. Peciña et al.

    Opioid site in nucleus accumbens shell mediates eating and hedonic ‘liking’ for food: map based on microinjection Fos plumes

    Brain Research

    (2000)
  • T.E. Robinson et al.

    The neural basis of drug craving: an incentive-sensitization theory of addiction

    Brain Research. Brain Research Reviews

    (1993)
  • B.L. Thomas et al.

    Adrenalectomy eliminates the extinction spike in autoshaping with rats

    Physiology & Behavior

    (2001)
  • A. Tomie et al.

    Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse

    Brain Research Reviews

    (2008)
  • A. Tomie et al.

    Autoshaping induces ethanol drinking in nondeprived rats: evidence of long-term retention but no induction of ethanol preference

    Pharmacology, Biochemistry, and Behavior

    (2004)
  • A. Tomie et al.

    Autoshaping of ethanol drinking in rats: effects of ethanol concentration and trial spacing

    Alcohol

    (2003)
  • J.M. Uslaner et al.

    The attribution of incentive salience to a stimulus that signals an intravenous injection of cocaine

    Behavioural Brain Research

    (2006)
  • A.R. Willey et al.

    Effects of ethanol administration on corticosterone levels in adolescent and adult rats

    Alcohol

    (2012)
  • C.J. Auger et al.

    Progestin receptor-mediated reduction of anxiety-like behavior in male rats

    PLoS One

    (2008)
  • S. Bava et al.

    Longitudinal changes in white matter integrity among adolescent substance users

    Alcoholism: Clinical and Experimental Research

    (2013)
  • M.A. Broadwater et al.

    Tone conditioning potentiates rather than overshadows context fear in adult animals following adolescent ethanol exposure

    Developmental Psychobiology

    (2013)
  • S.A. Brown et al.

    Adolescence and the trajectory of alcohol use: basic to clinical studies

    Annals of the New York Academy of Sciences

    (2004)
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