Absence of effects of intermittent access to alcohol on negative affective and anxiety-like behaviors in male and female C57BL/6J mice

Rinker, Jennifer A.; Marcus, Madison M.; Mulholland, Patrick J.

doi:10.1016/j.alcohol.2020.07.011

Cited by 23 publications

(27 citation statements)

References 58 publications

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“…Because female mice drink more ethanol than male mice, it is possible that the divergent functional networks are caused by differences in the amount of ethanol consumed. Consistent with previous reports (Bloch et al, 2020;Hwa et al, 2011;Sneddon et al, 2019;Yoneyama et al, 2008), the high-drinking female mice that were included in this c-Fos mapping study consumed more alcohol during the 4 th week of drinking compared with the high-drinking male mice. This effect of sex on ethanol intake was also observed during the short drinking episode on the day that brains were extracted and prepared for whole-brain c-Fos mapping.…”

Section: Discussionsupporting

confidence: 90%

“…After acclimatization, mice were housed individually and were given 24 h intermittent access to alcohol (IAA; 20% v/v) and water from 9 am to 9 am with 24 or 48 h between drinking sessions (Mondays, Wednesdays, and Fridays) (Bloch et al, 2020;Cannady et al, 2020;Rinker et al, 2017;Zamudio et al, 2020). Mice were subjected to the IAA model for 4 weeks with 3 drinking sessions/week.…”

Section: Two-bottle Choice Intermittent Ethanol Accessmentioning

confidence: 99%

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Divergent sex differences in functional brain connectivity networks in excessively drinking C57BL/6J mice

Smith

et al. 2021

Preprint

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Individuals with alcohol use disorder continue to drink in excess despite the health and societal consequences, and the rate of problematic drinking and alcohol-related harms is increased in women. Clinical imaging studies report widespread adaptations in brain structure after chronic, heavy drinking, and alcohol-related cues enhance brain reactivity in reward-related regions. In rodents, alcohol drinking induces expression of the immediate early gene c-Fos, which can be a marker of cellular activity, across multiple brain regions. Recent evidence also suggests that abstinence from chronic intermittent alcohol exposure can produce mesoscale changes in c-Fos expression. However, there is a substantial gap in our understanding of how excessive drinking affects functional connectivity networks to influence alcohol-seeking behaviors. For this study, male and female C57BL/6J mice were given access to either water or a choice between water and ethanol in the intermittent access drinking model for 4 weeks. After a short-access drinking session, whole brains from high alcohol drinking male and female mice and water drinking controls were then subjected to c-Fos immunolabeling, iDISCO+ clearing, light sheet imaging, and whole-brain c-Fos mapping. Correlation matrices were then generated and graph theoretical statistical approaches were used to determine changes in functional connectivity across sex and drinking condition. We observed robust sex differences in the network of c-Fos+ cells in water drinking mice, and excessive alcohol drinking produce divergent and robust changes in functional network connectivity in male and female mice. In addition, these analyses identified novel hub regions in excessively drinking mice that were unique for each sex. In conclusion, the whole-brain c-Fos mapping analysis identified sex difference in functional network connectivity and unique and understudied regions that may play a critical role in controlling excessive ethanol drinking in male and female mice.

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Section: Discussionsupporting

confidence: 90%

Section: Two-bottle Choice Intermittent Ethanol Accessmentioning

confidence: 99%

Divergent sex differences in functional brain connectivity networks in excessively drinking C57BL/6J mice

Smith

et al. 2021

Preprint

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“…The reduced anogenital sniffing in male P301S mice may also be interpreted as reduced anxiety-like behavior in the presence of a novel mouse. We and others, however, have observed similar changes in behavior following stress and in withdrawal from drugs in C57BL/6J mice, which has led us to interpret these changes as behavioral disinhibition (Osborn et al, 1998; Lacroix et al, 2000; Mozhui et al, 2010; Masneuf et al, 2014; Fish et al, 2018; Lowery-Gionta et al, 2018; Bloch et al, 2020; Bravo et al, 2020) Interestingly we did not see a significant main effect of treatment nor genotype by treatment interaction in male mice across these assays. It is possible the IA paradigm is insufficient to dysregulate negative affective behavior.…”

Section: Discussionsupporting

confidence: 73%

Effects of Long-Term Alcohol Consumption on Behavior in the P301S (Line PS19) Tauopathy Mouse Model

Catavero

Marsh

Downs

et al. 2022

Preprint

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Alcohol consumption and misuse remain prevalent public health issues with recent reports of increased heavy consumption in older populations in the United States. Several studies have identified alcohol consumption as a risk factor for developing multiple forms of dementia. The behavioral and psychological symptoms of dementia (BPSD), such as changes in affective behavior (e.g. anxiety), precede and coincide with cognitive decline. While many studies have characterized the intersection of alcohol use and affective behaviors, little is known regarding alcohol consumption and BPSD. This study characterizes the impact of long-term alcohol consumption on various behaviors in the P301S (line PS19) tauopathy mouse model. Male and female P301S and littermate control mice underwent two-bottle choice intermittent access to alcohol for sixteen weeks starting at 12 weeks of age. There were no significant differences in total ethanol consumption between wildtype and P301S mice of the same sex; however, drinking behavior differed among genotypes, and female mice of each genotype drank significantly more ethanol than males of each genotype. Following drinking studies, mice were run through a battery of behavioral tests during a period of forced abstinence, including approach/avoidance assays, social behavior tests, and memory and cognition tests. Across these tests we observed differences between groups due to genotype, alcohol history, and interactions between alcohol exposure and genotype. These differences were not always consistent between the sexes. In total, this study reveals significant alcohol-tauopathy interactions in subsequent behavior, which may have implications for understanding how alcohol may impact BPSD in conditions associated with tauopathy like Alzheimer's disease and frontotemporal dementia.

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“…Studies have found varying results with regards to sex differences in anxiety-like behavior. Some studies report that male mice exhibit increased latency to eat in the NSF (Jury et al, 2017, Bloch et al, 2020, whereas other studies using Wistar rats report the opposite, with females exhibiting increased latency to eat compared to males (De Oliveira Sergio et al, 2021). Additionally, other studies saw no sex differences in anxiety-like behavior in the NSF in both Sprague Dawley (Wright et al, 2019) and Wistar (Olivier et al, 2008) rats.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Affective States and Association with Voluntary Ethanol Intake in Sprague Dawley Rats

Quadir

Arleth

Jahad

et al. 2021

Preprint

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Alcohol use disorders (AUDs) are a major problem across the United States. While AUD remains a complex human condition, it is difficult to isolate the directionality of anxiety and ethanol (EtOH) drinking from outside influences. The present study sought to investigate the relationship between affective states and EtOH intake using male and female Sprague Dawley rats. Using complementary tests of anxiety- and depressive-like behavior, we found sex- and test-specific differences in basal affective behavior such that females displayed enhanced anxiety-like behavior in the Splash Test and males displayed enhanced anxiety-like behavior in the Novelty Suppressed Feeding Test. Although there were no sex differences in EtOH intake and no correlation between anxiety-like behavior and subsequent EtOH intake, we did find that depressive-like behavior predicted future EtOH intake in females rats only. In addition, we observed an increase in depressive-like behavior is male rats in both the water and EtOH drinking groups. Furthermore, anxiety-like behavior, but not depressive-like behavior predicted subsequent EtOH intake in female rats. Lastly, we found a history of EtOH intake decreased pain thresholds in male and female rats. Together, these experiments provide important information on the complex interaction between negative affect and alcohol intake and how these two contexts reciprocally do, or do not, influence each other in a sex-specific manner.

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Absence of effects of intermittent access to alcohol on negative affective and anxiety-like behaviors in male and female C57BL/6J mice

Cited by 23 publications

References 58 publications

Divergent sex differences in functional brain connectivity networks in excessively drinking C57BL/6J mice

Divergent sex differences in functional brain connectivity networks in excessively drinking C57BL/6J mice

Effects of Long-Term Alcohol Consumption on Behavior in the P301S (Line PS19) Tauopathy Mouse Model

Sex Differences in Affective States and Association with Voluntary Ethanol Intake in Sprague Dawley Rats

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