Impact of adolescent intermittent ethanol exposure in male and female rats on social drinking and neuropeptide gene expression.

Background: Alcohol use during adolescence can alter maturational changes that occur in brain regions associated with social and emotional responding. Our previous studies have shown that adult male, but not female rats demonstrate social anxiety-like alterations and enhanced sensitivity to ethanol-induced social facilitation following adolescent intermittent ethanol exposure (AIE). These consequences of AIE may influence adult social drinking in a sex-specific manner.

Adolescent intermittent ethanol exposure does not alter responsiveness to ifenprodil or expression of vesicular GABA and glutamate transporters.

Adolescent intermittent ethanol (AIE) exposure in the rat results in a retention of adolescent-like responsiveness to ethanol into adulthood characterized by enhanced sensitivity to socially facilitating and decreased sensitivity to socially suppressing and aversive effects. Similar pattern of responsiveness to social and aversive effects of the selective glutamate NMDA NR2B receptor antagonist ifenprodil is evident in adolescent rats, suggesting that AIE would also retain this pattern of ifenprodil sensitivity into adulthood. Social (Experiment 1) and aversive (measured via conditioned taste aversion; Experiment 2) effects of ifenprodil were assessed in adult male and female rats following AIE exposure.

The effects of age, sex, and handling on behavioral parameters in the multivariate concentric square field™ test.

The multivariate concentric square field™ (MCSF) is a complex and ethologically relevant apparatus that is designed to measure several behavioral parameters within the same test session including risk-taking, risk-assessment, shelter-seeking (anxiety relieving), exploration, and general activity. While several studies have behaviorally and pharmacologically validated the use of the MCSF in adults, far fewer have used adolescents. Given the well-established link between adolescence and risk-taking, it is important to validate use of the MCSF in adolescence.

Rats exposed to intermittent ethanol during late adolescence exhibit enhanced habitual behavior following reward devaluation.

The brain undergoes substantial maturation during adolescence, and repeated exposure to ethanol at this time has been shown to result in long-lasting behavioral and neural consequences. During the broad period of adolescence, different neuronal populations and circuits are refined between early and late adolescence, suggesting the possibility that ethanol exposure at these differing times may lead to differential outcomes. The goal of the current study was to evaluate the impact of adolescent intermittent ethanol (AIE) during early and late adolescence on the formation of goal-directed and habitual behavior in adulthood.

Adolescent Intermittent Ethanol Exposure Effects on Kappa Opioid Receptor Mediated Dopamine Transmission: Sex and Age of Exposure Matter.

Underage alcohol drinking increases the risk of developing alcohol use disorder (AUD). In rodents, adolescent ethanol exposure augments ethanol consumption and anxiety-like behavior while reducing social interaction. However, the underlying mechanisms driving these adaptations are unclear.

General Anesthetic Exposure During Early Adolescence Persistently Alters Ethanol Responses.

Background: Adolescent alcohol abuse can lead to behavioral dysfunction and chronic, relapsing alcohol use disorder (AUD) in adulthood. However, not all adolescents that consume alcohol will develop an AUD; therefore, it is critical to identify neural and environmental risk factors that contribute to increases in susceptibility to AUDs following adolescent alcohol (ethanol [EtOH]) exposure. We previously found that adolescent anesthetic exposure led to strikingly similar behavioral and neural effects as adolescent alcohol exposure.

Timing Eclipses Amount: The Critical Importance of Intermittency in Alcohol Exposure Effects.

Frequency and duration of ethanol (EtOH) exposures influence the consequences of those experiences, with evidence building from basic science studies in rats and mice that intermittent alcohol access (IAA) typically produces a greater escalation of EtOH intake than more continuous alcohol access (CAA). IAA also better simulates human use patterns where alcohol levels typically clear from the body between periods of use. A variety of mechanisms have been proposed to contribute to the enhanced intake of EtOH induced by IAA, including a possible attenuation in the aversive effects of EtOH, although further studies are needed to address this and other possibilities.

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.

Adolescent but not adult Sprague-Dawley rats display goal-directed responding after reward devaluation.

Alcohol drinking is typically initiated in adolescence, with use sometimes escalating to problematic levels. Escalation of drinking is often associated with a shift in drinking motives, with goal-directed initial use later transitioning to more habitual behavior. This study assessed whether adolescents are more sensitive than adults to habit formation when indexed via insensitivity to reward devaluation in an operant task for food reward.

Mechanisms of Persistent Neurobiological Changes Following Adolescent Alcohol Exposure: NADIA Consortium Findings.

The Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium has focused on the impact of adolescent binge drinking on brain development, particularly on effects that persist into adulthood. Adolescent binge drinking is common, and while many factors contribute to human brain development and alcohol use during adolescence, animal models are critical for understanding the specific consequences of alcohol exposure during this developmental period and the underlying mechanisms. Using adolescent intermittent ethanol (AIE) exposure models, NADIA investigators identified long-lasting AIE-induced changes in adult behavior that are consistent with observations in humans, such as increased alcohol drinking, increased anxiety (particularly social anxiety), increased impulsivity, reduced behavioral flexibility, impaired memory, disrupted sleep, and altered responses to alcohol.

Excitatory/inhibitory balance across ontogeny contributes to age-specific behavioral outcomes of ethanol-like challenge in conditioned taste aversion.

Adolescent-typical sensitivities to ethanol (EtOH) are characterized in part by reduced sensitivity to EtOH's aversive effects. Rodent studies have shown that adolescents are less sensitive than adults to aversive properties of EtOH in a conditioned taste aversion (CTA) paradigm. To the extent that EtOH exerts antagonist-like actions upon glutamate receptors and/or agonist-like actions upon γ-aminobutyric acid (GABA) receptors, age differences in excitatory/inhibitory balance may regulate age-specific EtOH sensitivities, such as attenuated sensitivity of adolescents to EtOH aversion.

General anesthetic exposure in adolescent rats causes persistent maladaptations in cognitive and affective behaviors and neuroplasticity.

Accumulating evidence indicates that exposure to general anesthetics during infancy and childhood can cause persistent cognitive impairment, alterations in synaptic plasticity, and, to a lesser extent, increased incidence of behavioral disorders. Unfortunately, the developmental parameters of susceptibility to general anesthetics are not well understood. Adolescence is a critical developmental period wherein multiple late developing brain regions may also be vulnerable to enduring general anesthetic effects.

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.

Prenatal ethanol exposure attenuates sensitivity to the aversive effects of ethanol in adolescence and increases adult preference for a 5% ethanol solution in males, but not females.

The present set of experiments investigated the effects of a moderate dose of ethanol (2 g/kg; 20% v/v intragastrically) during late gestation (G17-20 [gestational day]) on ethanol-induced conditioned taste aversion (CTA) in adolescence, and on ethanol consumption during adolescence and early adulthood. In experiment 1, male and female Sprague-Dawley rats were given 30-min access to a sweetened "supersaccharin" (SS) solution or sodium chloride (NaCl), followed by an intraperitoneal injection of 20% ethanol (0, 1, 1.25, or 1.

Binge Drinking's Effects on the Developing Brain-Animal Models.

Adolescence typically is a time of experimentation, including alcohol use and, particularly, binge drinking. Because the brain is still developing during adolescence, such exposure could have long-lasting effects. Animal models and adolescent intermittent ethanol exposure (AIE) paradigms have been used to help elucidate the consequences of adolescent binge drinking.

Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats.

The dynorphin/kappa opioid receptor (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adult rodents, there is growing evidence suggesting that this system is ontogenetically regulated.

Adolescent intermittent ethanol exposure: Effects on pubertal development, novelty seeking, and social interaction in adulthood.

Alcohol use initiated early in adolescence is a major predictor for the development of alcohol use disorders. This risk may be increased when drinking is initiated around the time of puberty, given evidence of bidirectional relationships between alcohol and gonadal hormones. The current study examined the effects of adolescent intermittent ethanol exposure (AIE) on pubertal timing and expression of novelty-seeking and peer-directed behaviors as well as neural correlates of these behaviors.

Oxytocin and vasopressin modulation of social anxiety following adolescent intermittent ethanol exposure.

Rationale: Adolescent intermittent ethanol exposure (AIE) produces lasting, sex-specific social anxiety-like alterations in male, but not female rats. Oxytocin (OXT) and vasopressin (AVP) brain systems play opposite roles in regulating social preference/avoidance, with OXT increasing approach to, and AVP increasing avoidance of social stimuli.

Objectives: To test the hypothesis that social anxiety-like alterations seen in adult males after AIE are associated with a shift in the balance between OXT and AVP toward AVP, effectiveness of pharmacological activation of the OXT system and blockade of endogenous activity at AVP receptors for reversing AIE-induced social anxiety-like alterations was assessed, along with examination of the effects of AIE on OXT, vasopressin V1a, and V1b receptor (OXT-R, V1a-R, and V1b-R) surface expression in the hypothalamus.

Effects of AMPA receptor antagonist, NBQX, and extrasynaptic GABA agonist, THIP, on social behavior of adolescent and adult rats.

Adolescence is characterized by high significance of social interactions, along with a propensity to exhibit social facilitating effects of ethanol while being less sensitive than adults to the inhibition of social behavior that emerges at higher doses of ethanol. Among the neural characteristics of adolescence are generally enhanced levels of glutamatergic (especially NMDA receptor) activity relative to adults, whereas the GABA system is still developmentally immature. Activation of NMDA receptors likely plays a role in modulation of social behavior in adolescent animals as well as in socially facilitating and suppressing effects of ethanol.

Author Correction: Effects of adolescent alcohol consumption on the brain and behaviour.

In the initially published version of this article, the following sentence was incorrect: "Studies that have compared equivalent exposures to alcohol in adolescent and adult animals have found that the effects of alcohol exposure during adolescence are generally not evident or are less pronounced than after comparable alcohol exposure in adulthood". The sentence should have read: "Studies that have compared equivalent exposures to alcohol in adolescent and adult animals have found that the effects of alcohol exposure during adulthood are generally not evident or are less pronounced than after comparable alcohol exposure in adolescence". The sentence has been corrected in the HTML and PDF versions of the article.

Effects of adolescent alcohol consumption on the brain and behaviour.

Per occasion, alcohol consumption is higher in adolescents than in adults in both humans and laboratory animals, with changes in the adolescent brain probably contributing to this elevated drinking. This Review examines the contributors to and consequences of the use of alcohol in adolescents. Human adolescents with a history of alcohol use differ neurally and cognitively from other adolescents; some of these differences predate the commencement of alcohol consumption and serve as potential risk factors for later alcohol use, whereas others emerge from its use.

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.

Subjective alcohol responses in a cross-sectional, field-based study of adolescents and young adults: Effects of age, drinking level, and dependence/consequences.

Background: Adolescents are physically, cognitively, socially, and emotionally different than adults in ways that may partially explain why alcohol misuse typically develops during this period. Ample animal-science evidence and nascent ecological evidence points toward developmentally limited differences in sensitivity to alcohol's stimulatory and sedative effects. Field-based research methods were used to test for such age-related differences in a sample of adolescents through young adults.

Reward-centricity and attenuated aversions: An adolescent phenotype emerging from studies in laboratory animals.

Adolescence is an evolutionarily conserved developmental period, with neural circuits and behaviors contributing to the detection, procurement, and receipt of rewards bearing similarity across species. Studies with laboratory animals suggest that adolescence is typified by a "reward-centric" phenotype-an increased sensitivity to rewards relative to adults. In contrast, adolescent rodents are reportedly less sensitive to the aversive properties of many drugs and naturally aversive stimuli.