Ethanol-induced anxiolysis and neuronal activation in the amygdala and bed nucleus of the stria terminalis

Sharko, Amanda C.; Kaigler, Kris F.; Fadel, Jim R.; Wilson, Marlene A.

doi:10.1016/j.alcohol.2015.11.001

Cited by 39 publications

(22 citation statements)

References 45 publications

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“…Specifically, scopolamine increased the time zebrafish spent near the novel object in the novel approach test, increased the time fish spent in the top zone of the novel tank diving test, and decreased shoal cohesion. All of these effects are consistent with well-established anxiolytic drugs in other zebrafish studies 12 , 20 , 27 , and cannot be attributed to unwanted side effects on the pupil that might affect light avoidance. Because the anxiolytic effect of scopolamine on zebrafish behaviour is consistent with what is seen in humans 4 – 6 , we conclude zebrafish is a suitable model organism to test potential anxiolytic compounds for eventual human use.…”

Section: Resultssupporting

confidence: 86%

“…There are many well-validated tests of anxiety-like behaviour in zebrafish (for review see references 12 , 27 ) yet to date there has only been one study that examined the effects of scopolamine on anxiety in zebrafish. Cho and colleagues (2011) 15 placed zebrafish in a 2-L tank with a light source suspended above the water and anxiety was measured as light-avoidance behavior.…”

Section: Discussionmentioning

confidence: 99%

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Establishing zebrafish as a model to study the anxiolytic effects of scopolamine

Hamilton

Morrill

Lucas

et al. 2017

Sci Rep

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Scopolamine (hyoscine) is a muscarinic acetylcholine receptor antagonist that has traditionally been used to treat motion sickness in humans. However, studies investigating depressed and bipolar populations have found that scopolamine is also effective at reducing depression and anxiety symptoms. The potential anxiety-reducing (anxiolytic) effects of scopolamine could have great clinical implications for humans; however, rats and mice administered scopolamine showed increased anxiety in standard behavioural tests. This is in direct contrast to findings in humans, and complicates studies to elucidate the specific mechanisms of scopolamine action. The aim of this study was to assess the suitability of zebrafish as a model system to test anxiety-like compounds using scopolamine. Similar to humans, scopolamine acted as an anxiolytic in individual behavioural tests (novel approach test and novel tank diving test). The anxiolytic effect of scopolamine was dose dependent and biphasic, reaching maximum effect at 800 µM. Scopolamine (800 µM) also had an anxiolytic effect in a group behavioural test, as it significantly decreased their tendency to shoal. These results establish zebrafish as a model organism for studying the anxiolytic effects of scopolamine, its mechanisms of action and side effects.

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Section: Resultssupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Establishing zebrafish as a model to study the anxiolytic effects of scopolamine

Hamilton

Morrill

Lucas

et al. 2017

Sci Rep

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“…Most of the neurons in the BNST are GABAergic and activation of the BNST is generally anxiogenic ( Ch’ng et al, 2018 ). Alcohol decreases the excitability of the BNST, which is crucial to the anxiolytic properties of EtOH ( Leriche et al, 2008 ; Sharko et al, 2016 ). One of the ways that EtOH may be acting to reduce anxiety could be through increased expression of Gabra2 .…”

Section: Discussionmentioning

confidence: 99%

Sex and β-Endorphin Influence the Effects of Ethanol on Limbic Gabra2 Expression in a Mouse Binge Drinking Model

et al. 2018

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Binge drinking is a widespread problem linked to increased risk for alcohol-related complications, including development of alcohol use disorders. In the last decade, binge drinking has increased significantly, specifically in women. Clinically, sexually dimorphic effects of alcohol are well-characterized, however, the underlying mechanisms for these dimorphisms in the physiological and behavioral effects of alcohol are poorly understood. Among its many effects, alcohol consumption reduces anxiety via the inhibitory neurotransmitter GABA, most likely acting upon receptors containing the α-2 subunit (Gabra2). Previous research from our laboratory indicates that female mice lacking the endogenous opioid peptide β-endorphin (βE) have an overactive stress axis and enhanced anxiety-like phenotype, coupled with increased binge-like alcohol consumption. Because βE works via GABA signaling to reduce anxiety, we sought to determine whether sexually dimorphic binge drinking behavior in βE deficient mice is coupled with differences in CNS Gabra2 expression. To test this hypothesis, we used βE knock-out mice in a “drinking in the dark” model where adult male and female C57BL/6J controls (βE +/+) and βE deficient (βE -/-; B6.129S2-Pomctm1Low/J) mice were provided with one bottle of 20% ethanol (EtOH) and one of water (EtOH drinkers) or two bottles of water (water drinkers) 3 h into the dark cycle for four consecutive days. Following a binge test on day 4, limbic tissue was collected and frozen for subsequent qRT-PCR analysis of Gabra2 mRNA expression. Water-drinking βE +/+ females expressed more Gabra2 in central nucleus of the amygdala and the bed nucleus of the stria terminalis than males, but this sex difference was absent in the βE -/- mice. Genotype alone had no effect on alcohol consumption or drug-induced increase in Gabra2 expression. In contrast, βE expression had bi-directional effects in females: in wildtypes, Gabra2 mRNA was reduced by binge EtOH consumption, while EtOH increased expression in βE -/- females to levels commensurate with drug-naïve βE +/+ females. These results support the contention that βE plays a role in sexually dimorphic binge-like EtOH consumption, perhaps through differential expression of GABAA α2 subunits in limbic structures known to play key roles in the regulation of stress and anxiety.

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“…Extended binge drinking may produce anxiety-like behavior [6]. Previous studies demonstrate that acute alcohol may reduce the time rodents take to emerge from the dark to the light [63].…”

Section: Maladaptive Behaviors Following Binge Drinkingmentioning

confidence: 99%

Interneuronal δ-GABAA receptors regulate binge drinking and are necessary for the behavioral effects of early withdrawal

Melón

Nasman

John

et al. 2018

Neuropsychopharmacol

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Extensive evidence points to a role for GABAergic signaling in the amygdala in mediating the effects of alcohol, including presynaptic changes in GABA release, suggesting effects on GABAergic neurons. However, the majority of studies focus solely on the effects of alcohol on principal neurons. Here we demonstrate that δ-GABARs, which have been suggested to confer ethanol sensitivity, are expressed at a high density on parvalbumin (PV) interneurons in the basolateral amygdala (BLA). Thus, we hypothesized that δ-GABARs on PV interneurons may represent both an initial pharmacological target for alcohol and a site for plasticity associated with the expression of various behavioral maladaptations during withdrawal from binge drinking. To investigate this, we used a mouse model of voluntary alcohol intake (Drinking-in-the-Dark-Multiple Scheduled Access) to induce escalating heavy binge drinking and anxiety-like behavior in mice. This pattern of intake was associated with increased δ protein expression on parvalbumin positive interneurons in both the BLA and hippocampus. Loss of δ-GABARs specifically in PV interneurons (PV:δ) increased binge drinking behavior, reduced sensitivity to alcohol-induced motor incoordination, enhanced sensitivity to alcohol-induced hyperlocomotion and blocked the expression of withdrawal from binge drinking. This study is the first to demonstrate a role for δGABARs specifically in PV-expressing interneurons in modulating binge alcohol intake and withdrawal-induced anxiety.

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Ethanol-induced anxiolysis and neuronal activation in the amygdala and bed nucleus of the stria terminalis

Cited by 39 publications

References 45 publications

Establishing zebrafish as a model to study the anxiolytic effects of scopolamine

Establishing zebrafish as a model to study the anxiolytic effects of scopolamine

Sex and β-Endorphin Influence the Effects of Ethanol on Limbic Gabra2 Expression in a Mouse Binge Drinking Model

Interneuronal δ-GABAA receptors regulate binge drinking and are necessary for the behavioral effects of early withdrawal

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