Binge ethanol drinking associated with sex-dependent plasticity of neurons in the insula that project to the bed nucleus of the stria terminalis

Marino, Rosanna; Girven, Kasey S.; Figueiredo, Antonio; Navarrete, Jovana; Doty, Carolyn; Sparta, Dennis R.

doi:10.1016/j.neuropharm.2021.108695

Cited by 14 publications

(12 citation statements)

References 59 publications

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“…We injected ChABC into the anterior insula, but other insular subregions are involved in processing of negative information (41). The posterior insula plays a role in processing aversive states (42) and sex differences in posterior insula cortex connectivity with the bed nucleus of the stria terminalis (BNST) have been observed in mice (43) and humans (44). In addition, sexually dimorphic effects of ethanol on the posterior insula to BNST circuit have also been described (43).…”

Section: Discussionmentioning

confidence: 99%

Sexually dimorphic role for insular perineuronal nets in aversion-resistant alcohol consumption

Carvalho

Chen²,

Sutter³

et al. 2023

Front. Psychiatry

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Compulsive alcohol drinking is a key symptom of alcohol use disorder (AUD) that is particularly resistant to treatment. An understanding of the biological factors that underly compulsive drinking will allow for the development of new therapeutic targets for AUD. One animal model of compulsive alcohol drinking involves the addition of bitter-tasting quinine to an ethanol solution and measuring the willingness of the animal to consume ethanol despite the aversive taste. Previous studies have demonstrated that this type of aversion-resistant drinking is modulated in the insular cortex of male mice by specialized condensed extracellular matrix known as perineuronal nets (PNNs), which form a lattice-like structure around parvalbumin-expressing neurons in the cortex. Several laboratories have shown that female mice exhibit higher levels of aversion-resistant ethanol intake, but the role of PNNs in females in this behavior has not been examined. Here we compared PNNs in the insula of male and female mice and determined if disrupting PNNs in female mice would alter aversion-resistant ethanol intake. PNNs were visualized in the insula by fluorescent labeling with Wisteria floribunda agglutinin (WFA) and disrupted in the insula by microinjecting chondroitinase ABC, an enzyme that digests the chondroitin sulfate glycosaminoglycan component of PNNs. Mice were tested for aversion-resistant ethanol consumption by the addition of sequentially increasing concentrations of quinine to the ethanol in a two-bottle choice drinking in the dark procedure. PNN staining intensity was higher in the insula of female compared to male mice, suggesting that PNNs in females might contribute to elevated aversion-resistant drinking. However, disruption of PNNs had limited effect on aversion-resistant drinking in females. In addition, activation of the insula during aversion-resistant drinking, as measured by c-fos immunohistochemistry, was lower in female mice than in males. Taken together, these results suggest that neural mechanisms underlying aversion-resistant ethanol consumption differ in males and females.

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Section: Discussionmentioning

confidence: 99%

Sexually dimorphic role for insular perineuronal nets in aversion-resistant alcohol consumption

Carvalho

Chen²,

Sutter³

et al. 2023

Front. Psychiatry

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show abstract

“…We injected ChABC into the anterior insula, but other insular subregions are involved in processing of negative information (39). The posterior insula plays a role in processing aversive states (40) and sex differences in posterior insula cortex connectivity with the bed nucleus of the stria terminalis have been observed in mice (41) and humans (42). In addition, sexually dimorphic effects of ethanol on the posterior insula to BNST circuit have also been described (41).…”

Section: Discussionmentioning

confidence: 99%

“…The posterior insula plays a role in processing aversive states (40) and sex differences in posterior insula cortex connectivity with the bed nucleus of the stria terminalis have been observed in mice (41) and humans (42). In addition, sexually dimorphic effects of ethanol on the posterior insula to BNST circuit have also been described (41). The prefrontal cortex (PFC) is another possibility, since a PFC to nucleus accumbens circuit promotes aversionresistant ethanol intake in rats (14).…”

Section: Discussionmentioning

confidence: 99%

Sexually Dimorphic Role for Insular Perineuronal Nets in Aversion-Resistant Ethanol Consumption

Carvalho

Chen

Sutter

et al. 2023

Preprint

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Compulsive alcohol drinking is a key symptom of alcohol use disorder (AUD) that is particularly resistant to treatment. An understanding of the biological factors that underly compulsive drinking will allow for the development of new therapeutic targets for AUD. One animal model of compulsive alcohol drinking involves the addition of bitter-tasting quinine to an ethanol solution and measuring the willingness of the animal to consume ethanol despite the aversive taste. Previous studies have demonstrated that this type of aversion-resistant drinking is modulated in the insular cortex of male mice by specialized condensed extracellular matrix known as perineuronal nets (PNNs), which form a lattice-like structure around parvalbumin-expressing neurons in the cortex. Several laboratories have shown that female mice exhibit higher levels of aversion-resistant ethanol intake but the role of PNNs in females in this behavior has not been examined. Here we compared PNNs in the insula of male and female mice and determined if disrupting PNNs in female mice would alter aversion-resistant ethanol intake. PNNs were visualized in the insula by fluorescent labeling with Wisteria floribunda agglutinin (WFA) and disrupted in the insula by microinjecting chondroitinase ABC, an enzyme that digests the chondroitin sulfate glycosaminoglycan component of PNNs. Mice were tested for aversion-resistant ethanol consumption by the addition of sequentially increasing concentrations of quinine to the ethanol in a two-bottle choice drinking in the dark procedure. PNN staining intensity was higher in the insula of female compared to male mice, suggesting that PNNs in females might contribute to elevated aversion-resistant drinking. However, disruption of PNNs had limited effect on aversion-resistant drinking in females. In addition, activation of the insula during aversion-resistant drinking, as measured by c-fos immunohistochemistry, was lower in female mice than in males. Taken together, these results suggest that neural mechanisms underlying aversion-resistant ethanol consumption differ in males and females.

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“…Like the original Rhodes et al DID procedure [67], many researchers reporting on sex effects on ethanol drinking provide access to only one bottle during a DID session -a bottle of ethanol that replaces the water bottle [67,72,74,75,[77][78][79][80][81]84,85]. This 1-bottle procedure is preferred in studies for which achieving high BECs is more important than determining ethanol preferences by way of a ≥2-bottle procedure [73,82,83,112]; Rhodes et al found higher BECs, but not necessarily higher ethanol intakes, for the 1-over a 2-bottle drinking procedure in 8 inbred mouse strains (including C57BL/6J) [66].…”

Section: Sex-chromosome Complement (Scc) and Gonadal Sex (Gs) Interac...mentioning

confidence: 99%

“…Importantly, although sex differences observed in DID-based procedures typically show greater ethanol consumption in female mice than male mice [73][74][75][76][77][78][79], these sex differences are sometimes not detected [80][81][82][83][84], varied from one experiment to the next within a report [66,67,72,85] and/or show greater intake in males than females [71]. This suggests that some procedural factors that vary across research studies moderate sex effects on ethanol drinking behaviors.…”

Section: Introductionmentioning

confidence: 99%

Gonadal Sex and Sex-Chromosome Complement Interact to Affect Ethanol Consumption in Adolescent Four Core Genotypes Mice

Aarde

Bagley

Jentsch

2022

Preprint

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Background: Sex differences in ethanol consumption have been reported in both humans and laboratory rodents, but the independent/dependent contributions of genetic and hormonal sex‑biasing mechanisms to these phenotypes have not yet been fully explored. Methods: To examine the contributions of sex-chromosome complement (SCC) and gonadal sex (GS) to ethanol consumption, we studied adolescent (28-32 days old) four core genotypes (FCG) mice (C57BL/6J background; FCG model allows for independent assortment of GS and SCC) using a modified drinking-in-the-dark (DID) procedure. Mice were offered concurrent access to 20%, 10% and 0% ethanol (in water) in four daily 2-hour sessions. Consumption at the level of individual bouts was recorded. Results: Although all four genotype groups preferred the 20% ethanol over 10% and 0%, and showed similar consumption of the 10% and 0% solutions, the group rankings for consumption of the 20% ethanol solution were XX+testes > XY+testes > XY+ovaries > XX+ovaries. Thus, an interaction was observed between SCC and GS for which the simple effect of SCC was greatest in mice with ovaries (XY > XX) and the simple effect of GS was greatest in XX mice (testes > ovaries). Moreover, these effects varied in magnitude across and within drinking sessions. The behavioral microstructure of ethanol consumption (i.e., parameterization of within-session discriminable drinking bouts) support the validity of our 3-bottle modification of the DID procedure as a model of binge-like consumption as: (1) the consumption rate of the 20% ethanol solution was ~80 g EtOH/kg/h within a bout (~12 s/bout, ~3 bouts/session), (2) most of this ethanol consumption was completed in a single bout and (3) within-session ethanol consumption was greater earlier than later, indicating "front loading." Conclusions: These results indicate that SCC and GS interact on ethanol consumption in adolescent FCG mice on a C57BL/6J background to affect binge-like consumption from the very initiation of access and that these effects are dynamic as they varied both across and within sessions.

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Binge ethanol drinking associated with sex-dependent plasticity of neurons in the insula that project to the bed nucleus of the stria terminalis

Cited by 14 publications

References 59 publications

Sexually dimorphic role for insular perineuronal nets in aversion-resistant alcohol consumption

Sexually dimorphic role for insular perineuronal nets in aversion-resistant alcohol consumption

Sexually Dimorphic Role for Insular Perineuronal Nets in Aversion-Resistant Ethanol Consumption

Gonadal Sex and Sex-Chromosome Complement Interact to Affect Ethanol Consumption in Adolescent Four Core Genotypes Mice

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