Sex differences in the effects of adolescent intermittent ethanol exposure on exploratory and anxiety-like behavior in adult rats

Healey, Kati L.; Kibble, Sandra; Bell, Amelia; Kramer, George Franklin; Maldonado‐Devincci, Antoniette M.; Swartzwelder, H. Scott

doi:10.1016/j.alcohol.2021.11.002

Cited by 16 publications

(10 citation statements)

References 59 publications

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“…In humans, the average age of first drink is just over 17 (Caetano et al, 2014), which is approximately equivalent to the age of the mice at inception of the experiment (8 weeks) (Dutta and Sengupta, 2016;Wang et al, 2020), thus we are able to observe the motivation of a translational timepoint in which individuals begin to drink. In addition, while we did not explicitly examine age, other important and interesting studies have shown that intermittent alcohol exposure starting during earlier adolescence can have stronger changes in affectand motivation-related behavior than alcohol-exposed adults (Van Skike et al, 2015;Kim et al, 2019;Nentwig et al, 2019;Healey et al, 2022). Here, using the intermittent access paradigm, we described a stark change in lower preference, less alcohol-engaged mice, where intermittent alcohol was related to a behavior shift toward higher alcohol responding and more impulsivity.…”

Section: Discussionmentioning

confidence: 75%

Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice

Starski

Maulucci

Mead

et al. 2022

Front. Behav. Neurosci.

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Alcohol use disorder (AUD) is related to excessive binge alcohol consumption, and there is considerable interest in associated factors that promote intake. AUD has many behavioral facets that enhance inflexibility toward alcohol consumption, including impulsivity, motivation, and attention. Thus, it is important to understand how these factors might promote responding for alcohol and can change after protracted alcohol intake. Previous studies have explored such behavioral factors using responding for sugar in the 5-Choice Serial Reaction Time Task (5-CSRTT), which allows careful separation of impulsivity, attention, and motivation. Importantly, our studies uniquely focus on using alcohol as the reward throughout training and testing sessions, which is critical for beginning to answer central questions relating to behavioral engagement for alcohol. Alcohol preference and consumption in male C57BL/6 mice were determined from the first 9 sessions of 2-h alcohol drinking which were interspersed among 5-CSRTT training. Interestingly, alcohol preference but not consumption level significantly predicted 5-CSRTT responding for alcohol. In contrast, responding for strawberry milk was not related to alcohol preference. Moreover, high-preference (HP) mice made more correct alcohol-directed responses than low-preference (LP) during the first half of each session and had more longer reward latencies in the second half, with no differences when performing for strawberry milk, suggesting that HP motivation for alcohol may reflect "front-loading." Mice were then exposed to an Intermittent Access to alcohol paradigm and retested in 5-CSRTT. While both HP and LP mice increased 5-CSRTT responding for alcohol, but not strawberry milk, LP performance rose to HP levels, with a greater change in correct and premature responding in LP versus HP. Overall, this study provides three significant findings: (1) alcohol was a suitable reward in the 5-CSRTT, allowing dissection of impulsivity, attention, and Frontiers in Behavioral Neuroscience 01 frontiersin.org Starski et al. 10.3389/fnbeh.2022.968359 motivation in relation to alcohol drinking, (2) alcohol preference was a more sensitive indicator of mouse 5-CSRTT performance than consumption, and (3) intermittent alcohol drinking promoted behavioral engagement with alcohol, especially for individuals with less initial engagement.

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Section: Discussionmentioning

confidence: 75%

Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice

Starski

Maulucci

Mead

et al. 2022

Front. Behav. Neurosci.

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“…In humans, chronic alcohol use during adolescence is associated with persistent cognitive and affective deficits (Spear, 2018), as well as increased risk of developing alcohol use disorder in adulthood (Dawson et al, 2008). Studies in animal models using rats show persistent effects of AIE on some affective-like behaviors including ethanol drinking, anxiety-like behavior, impulsivity, behavioral flexibility, memory, sleep, and social anxiety (Crews et al, 2019; Dannenhoffer et al, 2018; Healey et al, 2022; Pandey et al, 2015; Robinson et al, 2021). Thus, the data from clinical, and some basic research studies, support the conclusion that binge-like ethanol exposure during adolescence creates a propensity toward affective dysregulation (Dannenhoffer et al, 2018; Gilpin, 2012; Healey et al, 2022; Pandey et al, 2015; Varlinskaya et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Studies in animal models using rats show persistent effects of AIE on some affective-like behaviors including ethanol drinking, anxiety-like behavior, impulsivity, behavioral flexibility, memory, sleep, and social anxiety (Crews et al, 2019; Dannenhoffer et al, 2018; Healey et al, 2022; Pandey et al, 2015; Robinson et al, 2021). Thus, the data from clinical, and some basic research studies, support the conclusion that binge-like ethanol exposure during adolescence creates a propensity toward affective dysregulation (Dannenhoffer et al, 2018; Gilpin, 2012; Healey et al, 2022; Pandey et al, 2015; Varlinskaya et al, 2017). However, to better understand the neurobehavioral mechanisms underlying persistent AIE effects on affective behavior, a more fine-grained analysis of the specific nature of AIE effects on several affective behaviors in multiple preclinical models is needed.…”

Section: Introductionmentioning

confidence: 99%

“…Sex differences in the acute and long-term effects of adolescent ethanol exposure are increasingly found in clinical and preclinical research. In rats, AIE exposure sex-specifically alters cognitive flexibility (Macht et al, 2020), affective behaviors (Healey et al, 2022; Varlinskaya et al, 2020), fear conditioning (Chandler et al, 2022), and social drinking (Towner et al, 2022) in adulthood. We recently showed that male and female AIE-exposed mice showed sex-specific patterns of subsequent ethanol drinking and withdrawal period-dependent differences in affective behaviors.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adolescent Intermittent Ethanol Exposure Alters Adult Exploratory and Affective Behaviors, and CerebellarGrin2BExpression in C57BL/6J Mice

Healey

Waters

Knight

et al. 2023

Preprint

Self Cite

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More than 90% of alcohol consumption by young people is in the pattern binge drinking. During adolescence, the brain undergoes maturational changes that influence alterations in behavior control, affective behaviors, and cerebellar brain volume and function in adulthood. We investigated long-term impacts of adolescent binge alcohol exposure on affective behaviors and cerebellar gene expression in male and female mice. We exposed C57BL/6J mice to adolescent intermittent ethanol (AIE) or air (control) vapor inhalation from postnatal day 28-42. After prolonged abstinence, in young adulthood we assessed behavior in the open field, light/dark, tail suspension, and forced swim stress tests to determine changes in affective behaviors including anxiety-like, depressive-like, and stress reactivity behavior. mRNA levels of FMR1 and other interacting gene expressions (Grin2a, Grin2B, Grm5, PSD-95, and Eaat1) were measured in the cerebellum of control and adult AIE-exposed mice. In adult AIE-exposed mice, we show decreased movement in the open field in both sexes and modest changes in females in anxiety-like behavior (center zone activity). In the forced swim stress test, adult AIE-exposed male mice spent less time immobile compared to their same-sex controls, indicative of sex-specific changes in stress reactivity. Male and female AIE-exposed mice showed increased Grin2B mRNA expression in the adult cerebellum compared to their same-sex controls. Together, these data show that adolescent binge-like ethanol exposure altered affective behaviors and modified Grin2B expression in adulthood. This indicates the cerebellum may serve as an important brain region that is susceptible to long-term molecular changes with adolescent alcohol exposure.

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Assessment of Hippocampal-Related Behavioral Changes in Adolescent Rats of both Sexes Following Voluntary Intermittent Ethanol Intake and Noise Exposure: A Putative Underlying Mechanism and Implementation of a Non-pharmacological Preventive Strategy

Buján,

D’Alessio,

Serra

et al. 2024

Neurotox Res

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Sex differences in the effects of adolescent intermittent ethanol exposure on exploratory and anxiety-like behavior in adult rats

Cited by 16 publications

References 59 publications

Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice

Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice

Adolescent Intermittent Ethanol Exposure Alters Adult Exploratory and Affective Behaviors, and CerebellarGrin2BExpression in C57BL/6J Mice

Assessment of Hippocampal-Related Behavioral Changes in Adolescent Rats of both Sexes Following Voluntary Intermittent Ethanol Intake and Noise Exposure: A Putative Underlying Mechanism and Implementation of a Non-pharmacological Preventive Strategy

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