Adolescent Ethanol Exposure: Anxiety-Like Behavioral Alterations, Ethanol Intake, and Sensitivity

Abstract

Adolescence is a developmental period associated with rapid age-specific physiological, neural, and hormonal changes. Behaviorally, human adolescents are characterized by age-typical increases in novelty-seeking and risk-taking, including the frequent initiation of alcohol and drug use. Alcohol use typically begins during early adolescence, and older adolescents often report high levels of alcohol consumption, commonly referred to as high-intensity drinking. Early-onset and heavy drinking during adolescence are associated with an increased risk of developing alcohol use disorders later in life. Yet, long-term behavioral consequences of adolescent alcohol use that might contribute to excessive drinking in adulthood are still not well understood. Recent animal research, however, using different exposure regimens and routes of ethanol administration, has made substantial progress in identifying the consequences of adolescent ethanol exposure that last into adulthood. Alterations associated with adolescent ethanol exposure include increases in anxiety-like behavior, impulsivity, risk-taking, and ethanol intake, although the observed alterations differ as a function of exposure regimens and routes of ethanol administration. Rodent studies have also shown that adolescent ethanol exposure produces alterations in sensitivity to ethanol, with these alterations reminiscent of adolescent-typical ethanol responsiveness. The goal of this mini-review article is to summarize the current state of animal research, focusing on the long-term consequences related to adolescent ethanol exposure, with a special emphasis on the behavioral alterations and changes to ethanol sensitivity that can foster high levels of drinking in adulthood.

Voluntary Adolescent-Onset Alcohol Drinking Fails to Influence Alcohol Consumption or Anxiety-Like Behaviour in Adulthood in Female Alcohol-Preferring Rats

“…2008 ). This relationship between adolescent and adult alcohol consumption has been found also in animal models ( Towner and Varlinskaya 2020 ).…”

“…2019 ). In contrast, as reviewed recently, approximately only a third of the studies using voluntary alcohol consumption models have been able to demonstrate increased alcohol intake when recorded later in adulthood ( Towner and Varlinskaya 2020 ). For example, intermittent 20% free-choice alcohol drinking by adolescent Wistar rats increased their alcohol consumption later in life ( Amodeo et al.…”

“…The critical factor determining the efficacy of adolescent alcohol exposure to influence behaviour in adulthood could be the blood alcohol concentration (BAC) attained upon alcohol administration. Generally, intermittent drinking paradigm or forced alcohol administration (injections, gavage) leading to BACs in the range of 100–200 mg/dl appears more successful in causing long-term behavioural changes than BACs of ~20–40 mg/dl measured during continual free-choice alcohol drinking ( Towner and Varlinskaya 2020 ). The subjects of the present study, alcohol-preferring AA rats, exhibit BACs of ~20–50 mg/dl during voluntary alcohol drinking bouts ( Nurmi et al.…”

Influence of Age and Genetic Background on Ethanol Intake and Behavioral Response Following Ethanol Consumption and During Abstinence in a Model of Alcohol Abuse

“…Indeed, even if human studies suggest that age of onset of alcohol use is associated with the risk to develop AUD later in life, recent systematic reviews suggest that this association is less consistent and might be driven by confounding factors, such as the history of alcohol problems in the family, preceding mental health problems, socioeconomic status, or genetic background ( Maimaris and McCambridge, 2014 ; Marshall, 2014 ; Kuntsche et al, 2016 ). Even animal studies on this issue are not always consistent ( Labots et al, 2018 ; Spear, 2018 ; Towner and Varlinskaya, 2020 ; Mugantseva et al, 2021 ) and therefore, further investigation is needed to help in clarifying the role of causality between early alcohol onset and increased risk of later AUD.…”

Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans

“…Using ethanol CTA, rodent studies have reliably demonstrated that adolescents are less sensitive to the aversive effects of ethanol as compared to adults [ 257 , 258 , 259 , 260 , 261 , 262 , 263 ]. In addition, animals exposed to ethanol as adolescents become relatively insensitive to the aversive effects of ethanol as adults [ 264 , 265 , 266 , 267 , 268 ]. Together, these findings suggest that exposure to ethanol during adolescence induces long-lasting decreases in sensitivity to the adverse effects of ethanol and may enable increased ethanol consumption, thus putting individuals at risk for the development of an AUD.…”