Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions

Forced abstinence (FA) from alcohol has been shown to produce a variety of anxiety- and depression-like symptoms in animal models. Somatostatin (SST) neurons, a subtype of GABAergic neurons found throughout the brain, are a novel neural target with potential treatment implications in affective disor...

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Main Authors: Nigel C. Dao, Malini Suresh Nair, Sarah N. Magee, J. Brody Moyer, Veronica Sendao, Dakota F. Brockway, Nicole A. Crowley
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Behavioral Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnbeh.2020.00086/full
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author Nigel C. Dao
Malini Suresh Nair
Malini Suresh Nair
Sarah N. Magee
J. Brody Moyer
Veronica Sendao
Dakota F. Brockway
Dakota F. Brockway
Nicole A. Crowley
Nicole A. Crowley
Nicole A. Crowley
author_facet Nigel C. Dao
Malini Suresh Nair
Malini Suresh Nair
Sarah N. Magee
J. Brody Moyer
Veronica Sendao
Dakota F. Brockway
Dakota F. Brockway
Nicole A. Crowley
Nicole A. Crowley
Nicole A. Crowley
author_sort Nigel C. Dao
collection DOAJ
description Forced abstinence (FA) from alcohol has been shown to produce a variety of anxiety- and depression-like symptoms in animal models. Somatostatin (SST) neurons, a subtype of GABAergic neurons found throughout the brain, are a novel neural target with potential treatment implications in affective disorders, yet their role in alcohol use disorders (AUD) remains to be explored. Here, we examined the neuroadaptations of SST neurons during forced abstinence from voluntary alcohol consumption. Following 6 weeks of two-bottle choice alcohol consumption and protracted forced abstinence, male and female C57BL/6J mice exhibited a heightened, but sex-specific, depressive-like behavioral profile in the sucrose preference test (SPT) and forced swim test (FST), without changes in anxiety-like behaviors in the elevated plus maze (EPM) and open field test (OFT). FST-induced cFos expressions in the prefrontal cortex (PFC) and ventral bed nucleus of the stria terminalis (vBNST) were altered in FA-exposed female mice only, suggesting a sex-specific effect of forced abstinence on the neural response to acute stress. SST immunoreactivity in these regions was unaffected by forced abstinence, while differences were seen in SST/cFos co-expression in the vBNST. No differences in cFos or SST immunoreactivity were seen in the lateral central nucleus of the amygdala (CEA) and the basolateral amygdala (BLA). Additionally, SST neurons in female mice displayed opposing alterations in the PFC and vBNST, with heightened intrinsic excitability in the PFC and diminished intrinsic excitability in the vBNST. These findings provide an overall framework of forced abstinence-induced neuroadaptations in these key brain regions involved in emotional regulation and processing.
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spelling doaj.art-1cbcd53b708d43639d7355019f7205b72022-12-22T02:06:17ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532020-05-011410.3389/fnbeh.2020.00086545286Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar RegionsNigel C. Dao0Malini Suresh Nair1Malini Suresh Nair2Sarah N. Magee3J. Brody Moyer4Veronica Sendao5Dakota F. Brockway6Dakota F. Brockway7Nicole A. Crowley8Nicole A. Crowley9Nicole A. Crowley10Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, United StatesDepartment of Biobehavioral Health, Pennsylvania State University, University Park, PA, United StatesDepartment of Biology, Pennsylvania State University, University Park, PA, United StatesDepartment of Biology, Pennsylvania State University, University Park, PA, United StatesDepartment of Biology, Pennsylvania State University, University Park, PA, United StatesDepartment of Biology, Pennsylvania State University, University Park, PA, United StatesDepartment of Biobehavioral Health, Pennsylvania State University, University Park, PA, United StatesNeuroscience Curriculum, Pennsylvania State University, University Park, PA, United StatesDepartment of Biobehavioral Health, Pennsylvania State University, University Park, PA, United StatesDepartment of Biology, Pennsylvania State University, University Park, PA, United StatesNeuroscience Curriculum, Pennsylvania State University, University Park, PA, United StatesForced abstinence (FA) from alcohol has been shown to produce a variety of anxiety- and depression-like symptoms in animal models. Somatostatin (SST) neurons, a subtype of GABAergic neurons found throughout the brain, are a novel neural target with potential treatment implications in affective disorders, yet their role in alcohol use disorders (AUD) remains to be explored. Here, we examined the neuroadaptations of SST neurons during forced abstinence from voluntary alcohol consumption. Following 6 weeks of two-bottle choice alcohol consumption and protracted forced abstinence, male and female C57BL/6J mice exhibited a heightened, but sex-specific, depressive-like behavioral profile in the sucrose preference test (SPT) and forced swim test (FST), without changes in anxiety-like behaviors in the elevated plus maze (EPM) and open field test (OFT). FST-induced cFos expressions in the prefrontal cortex (PFC) and ventral bed nucleus of the stria terminalis (vBNST) were altered in FA-exposed female mice only, suggesting a sex-specific effect of forced abstinence on the neural response to acute stress. SST immunoreactivity in these regions was unaffected by forced abstinence, while differences were seen in SST/cFos co-expression in the vBNST. No differences in cFos or SST immunoreactivity were seen in the lateral central nucleus of the amygdala (CEA) and the basolateral amygdala (BLA). Additionally, SST neurons in female mice displayed opposing alterations in the PFC and vBNST, with heightened intrinsic excitability in the PFC and diminished intrinsic excitability in the vBNST. These findings provide an overall framework of forced abstinence-induced neuroadaptations in these key brain regions involved in emotional regulation and processing.https://www.frontiersin.org/article/10.3389/fnbeh.2020.00086/fullforced abstinencealcoholsexstresssomatostatinprefrontal cortex
spellingShingle Nigel C. Dao
Malini Suresh Nair
Malini Suresh Nair
Sarah N. Magee
J. Brody Moyer
Veronica Sendao
Dakota F. Brockway
Dakota F. Brockway
Nicole A. Crowley
Nicole A. Crowley
Nicole A. Crowley
Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions
Frontiers in Behavioral Neuroscience
forced abstinence
alcohol
sex
stress
somatostatin
prefrontal cortex
title Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions
title_full Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions
title_fullStr Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions
title_full_unstemmed Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions
title_short Forced Abstinence From Alcohol Induces Sex-Specific Depression-Like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions
title_sort forced abstinence from alcohol induces sex specific depression like behavioral and neural adaptations in somatostatin neurons in cortical and amygdalar regions
topic forced abstinence
alcohol
sex
stress
somatostatin
prefrontal cortex
url https://www.frontiersin.org/article/10.3389/fnbeh.2020.00086/full
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