Effects of ethanol exposure during adolescence or in adulthood on Pavlovian conditioned approach in Sprague-Dawley rats
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)
- et al.
Autoshaping in adolescence enhances sign-tracking behavior in adulthood: impact on ethanol consumption
Pharmacology, Biochemistry, and Behavior
(2011) - et al.
Environmental enrichment reduces attribution of incentive salience to a food-associated stimulus
Behavioural Brain Research
(2012) - et al.
What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?
Brain Research. Brain Research Reviews
(1998) - et al.
Parsing reward
Trends in Neurosciences
(2003) Ethanol and brain plasticity: receptors and molecular networks of the postsynaptic density as targets of ethanol
Pharmacology & Therapeutics
(2003)- et al.
Periadolescent ethanol exposure reduces adult forebrain ChAT+IR neurons: correlation with behavioral pathology
Neuroscience
(2011) - et al.
Individual differences in the attribution of incentive salience to reward-related cues: Implications for addiction
Neuropharmacology
(2009) - et al.
A food predictive cue must be attributed with incentive salience for it to induce c-fos mRNA expression in cortico-striatal-thalamic brain regions
Neuroscience
(2011) - et al.
Individual differences in the attribution of incentive salience to a reward-related cue: influence on cocaine sensitization
Behavioural Brain Research
(2008) - et al.
Age at onset of alcohol use and its association with DSMIV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey
Journal of Substance Abuse
(1997)