Adolescent Ethanol Exposure Alters Cholinergic Function and Apical Dendritic Branching Within the Orbital Frontal Cortex

Kipp, B.T.; Nunes, Polliana Toledo; Galaj, Ewa; B, Hitchcock; T, Nasra; K, Poynor; Heide, Solveig; Reitz, Nicole L.; Savage, Lisa M.

doi:10.1016/j.neuroscience.2021.08.014

Cited by 12 publications

(17 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alterations of the OFC following AIE have been recently identified. For example, AIE leads to reduced cholinergic markers and lower acetylcholine release in the OFC during a spontaneous alternation task, although these results were similar between sexes ( Kipp et al, 2021 ). AIE also results in increased neuroimmune signaling in the OFC of males ( Vetreno et al, 2013 ), however this was not assessed in females.…”

Section: Discussionmentioning

confidence: 95%

“…Preclinical rodent models have identified several long-lasting behavioral impairments associated with adolescent alcohol (ethanol) exposure ( Crews et al, 2019 ), including, but not limited to, increases in anxiety-like behavior ( Kyzar et al, 2019 ; Sakharkar et al, 2019 ; Varlinskaya et al, 2020 ), reduced learning, memory, and cognitive flexibility ( Gass et al, 2014 ; Fernandez et al, 2017 ; Fernandez and Savage, 2017 ; Rico-Barrio et al, 2019 ; Macht et al, 2020 ; Varlinskaya et al, 2020 ), and also increased risk-taking ( Nasrallah et al, 2011 ; Clark et al, 2012 ; Kruse et al, 2017 ). These behavioral impairments are also associated with numerous neurobiological changes such as decreased acetylcholine markers ( Vetreno and Crews, 2018 ; Vetreno et al, 2020 ; Kipp et al, 2021 ), increased neural inflammation ( Vetreno and Crews, 2012 ; Vetreno et al, 2017 ; Vetreno and Crews, 2018 ; Macht et al, 2020 ; Vetreno et al, 2020 ), and dysregulated epigenetic regulators ( Kokare et al, 2017 ; Kyzar et al, 2017 ; Kyzar et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Adolescent Intermittent Ethanol Exposure on Social Investigation, Social Preference, and Neuronal Activation in cFos-LacZ Male and Female Rats

2022

View full text Add to dashboard Cite

Adolescence is a sensitive developmental period during which alcohol use is often initiated and consumed in high quantities, often at binge or even high-intensity drinking levels. Our lab has repeatedly found that adolescent intermittent ethanol (AIE) exposure in rats results in long-lasting social impairments, specifically in males, however our knowledge of the neuronal underpinnings to this sex-specific effect of AIE is limited. The present study was designed to test whether social anxiety-like alterations in AIE-exposed males would be accompanied by alterations of neuronal activation across brain regions associated with social behavior, with AIE females demonstrating no social impairments and alterations in neuronal activation. Adolescent male and female cFos-LacZ transgenic rats on a Sprague-Dawley background were exposed to ethanol (4 g/kg, 25% v/v) or water via intragastric gavage every other day during postnatal days (P) 25–45 for a total of 11 exposures (n = 13 per group). Social behavior of adult rats was assessed on P70 using a modified social interaction test, and neuronal activation in brain regions implicated in social responding was assessed via β-galactosidase (β-gal) expression. We found that AIE exposure in males resulted in a significantly lower social preference coefficient relative to water-exposed controls, with no effect evident in females. Exposure-specific relationships between social behavior and neuronal activation were identified, with AIE eliminating correlations found in water controls related to social interaction, and eliciting negative correlations mainly in limbic regions in a sex-specific manner. AIE exposure in the absence of social testing was also found to differentially affect neural activity in the orbitofrontal cortex and central amygdala in males and females. These data suggest that AIE produces sex-specific social impairments that are potentially driven by differential neuronal activation states in regions important for social behavior, including the medial prefrontal and orbitofrontal cortices, nucleus accumbens, lateral septum, and central amygdala. Future studies should be focused on identification of specific neuronal phenotypes activated by interaction with a social partner in AIE-exposed subjects and their control counterparts.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Impact of Adolescent Intermittent Ethanol Exposure on Social Investigation, Social Preference, and Neuronal Activation in cFos-LacZ Male and Female Rats

2022

View full text Add to dashboard Cite

show abstract

“…Intermittent binge ethanol in male and female adolescent rats (PND 22–55, 5 g/kg, i.g.) did not alter total dendritic spine density or proportion of mature or immature spines in the OFC ( Kipp et al, 2021 ). However, the amount of apical dendrite branching was increased by binge ethanol exposure with sex-dependent differences in where along the dendrite the increased branching was found ( Kipp et al, 2021 ).…”

Section: Introductionmentioning

confidence: 89%

“…A few studies have used less stressful and intense ethanol administration paradigms and exposed animals to ethanol using intraperitoneal injections or gavage ( Risher et al, 2015 ; Mulholland et al, 2018 ; Galaj et al, 2020 ; Kipp et al, 2021 ; Pascual et al, 2021 ). In general, oral dosing of ethanol in adolescents decreased spine density.…”

Section: Introductionmentioning

confidence: 99%

Areas of Convergence and Divergence in Adolescent Social Isolation and Binge Drinking: A Review

Lodha

Brocato

Wolstenholme

2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Adolescence is a critical developmental period characterized by enhanced social interactions, ongoing development of the frontal cortex and maturation of synaptic connections throughout the brain. Adolescents spend more time interacting with peers than any other age group and display heightened reward sensitivity, impulsivity and diminished inhibitory self-control, which contribute to increased risky behaviors, including the initiation and progression of alcohol use. Compared to adults, adolescents are less susceptible to the negative effects of ethanol, but are more susceptible to the negative effects of stress, particularly social stress. Juvenile exposure to social isolation or binge ethanol disrupts synaptic connections, dendritic spine morphology, and myelin remodeling in the frontal cortex. These structural effects may underlie the behavioral and cognitive deficits seen later in life, including social and memory deficits, increased anxiety-like behavior and risk for alcohol use disorders (AUD). Although the alcohol and social stress fields are actively investigating the mechanisms through which these effects occur, significant gaps in our understanding exist, particularly in the intersection of the two fields. This review will highlight the areas of convergence and divergence in the fields of adolescent social stress and ethanol exposure. We will focus on how ethanol exposure or social isolation stress can impact the development of the frontal cortex and lead to lasting behavioral changes in adulthood. We call attention to the need for more mechanistic studies and the inclusion of the evaluation of sex differences in these molecular, structural, and behavioral responses.

show abstract

“…The cholinergic system is also vulnerable to adolescent alcohol use. Intermittent alcohol exposure via intragastric gavage throughout adolescence reduced cholinergic markers in the orbitofrontal cortex (OFC) of male and female Sprague Dawley rats ( Kipp et al, 2021 ) and in the basal forebrain male in Wistar rats ( Boutros et al, 2015 ). Dendritic branching complexity was altered in the OFC, though the location of compromised branching was different in alcohol-exposed males and females ( Kipp et al, 2021 ).…”

Section: Animal Studies Of Alcohol Exposurementioning

confidence: 99%

Adolescent Alcohol and Stress Exposure Rewires Key Cortical Neurocircuitry

et al. 2022

View full text Add to dashboard Cite

Human adolescence is a period of development characterized by wide ranging emotions and behavioral risk taking, including binge drinking (Konrad et al., 2013). These behavioral manifestations of adolescence are complemented by growth in the neuroarchitecture of the brain, including synaptic pruning (Spear, 2013) and increases in overall white matter volume (Perrin et al., 2008). During this period of profound physiological maturation, the adolescent brain has a unique vulnerability to negative perturbations. Alcohol consumption and stress exposure, both of which are heightened during adolescence, can individually and synergistically alter these neurodevelopmental trajectories in positive and negative ways (conferring both resiliency and susceptibility) and influence already changing neurotransmitter systems and circuits. Importantly, the literature is rapidly changing and evolving in our understanding of basal sex differences in the brain, as well as the interaction between biological sex and life experiences. The animal literature provides the distinctive opportunity to explore sex-specific stress- and alcohol- induced changes in neurocircuits on a relatively rapid time scale. In addition, animal models allow for the investigation of individual neurons and signaling molecules otherwise inaccessible in the human brain. Here, we review the human and rodent literature with a focus on cortical development, neurotransmitters, peptides, and steroids, to characterize the field’s current understanding of the interaction between adolescence, biological sex, and exposure to stress and alcohol.

show abstract

Adolescent Ethanol Exposure Alters Cholinergic Function and Apical Dendritic Branching Within the Orbital Frontal Cortex

Cited by 12 publications

References 65 publications

Impact of Adolescent Intermittent Ethanol Exposure on Social Investigation, Social Preference, and Neuronal Activation in cFos-LacZ Male and Female Rats

Impact of Adolescent Intermittent Ethanol Exposure on Social Investigation, Social Preference, and Neuronal Activation in cFos-LacZ Male and Female Rats

Areas of Convergence and Divergence in Adolescent Social Isolation and Binge Drinking: A Review

Adolescent Alcohol and Stress Exposure Rewires Key Cortical Neurocircuitry

Contact Info

Product

Resources

About