IL-1 receptor signaling in the basolateral amygdala modulates binge-like ethanol consumption in male C57BL/6J mice

Marshall, S. Alex; Casachahua, John; Rinker, Jennifer A.; Blose, Allyson K.; Lysle, Donald T.; Thiele, Todd E.

doi:10.1016/j.bbi.2015.09.006

Cited by 61 publications

(76 citation statements)

References 61 publications

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“…Adjacent sections have previously been analyzed for IL-1β (Marshall et al 2016a). Briefly, sections were rinsed in 0.1M PBS before endogenous peroxidases were quenched with 0.6% H 2 O 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Determining the neuroimmune response following binge-like drinking in the absence of dependence will tease apart the acute contributions of binge ethanol consumption on neuroimmune responses from those associated with neurodegeneration or other comorbidities associated with ethanol misuse. Recently, it has been shown that binge-like ethanol consumption during the DID paradigm is sufficient to elicit an increase in IL-1β in the amygdala indicating that even acute excessive ethanol consumption can cause dysregulation of the neuroimmune system (Marshall et al 2016a). However, the influence of alcohol on anti-inflammatory cytokines, like IL-10 and IL-4, have yet to be explored.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, it was determined that modulation of IL-1 signaling within the amygdala with curbs binge-like drinking (Marshall et al 2016a). This study seeks to determine if that effect was unique to IL-1 signaling or if other cytokines also modulate ethanol consumption.…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Marshall

McKnight

Blose

et al. 2016

J Neuroimmune Pharmacol

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Excessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile and alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the “drinking in the dark” (DID) paradigm. Furthermore, the ability of IL-10 to modulate ethanol consumption was tested using site-directed pharmacology. Immunohistochemistry analyses determined that ethanol decreased IL-10 by 50% in the basolateral amygdala (BLA) but had no effect on IL-4. Neither IL-10 nor IL-4 were altered seen in the central amygdala (CEA). Enzyme linked immunosorbent assays confirmed that IL-10 was decreased in the amygdala but not in the serum, suggesting changes of this cytokine with the DID paradigm is restricted to the central nervous system. Finally, bilateral infusions of IL-10 into the BLA, but not CeA, reduced binge-like drinking and corresponding blood ethanol concentrations without impacting either locomotor activity or anxiety-like behavioral correlates. Together, these data support the idea that alcohol abuse dysregulates specific anti-inflammatory cytokines; however, ameliorating alcohol-induced effects on cytokines, like IL-10, may prove to be an effective therapy in curbing excessive consumption.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Marshall

McKnight

Blose

et al. 2016

J Neuroimmune Pharmacol

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“…Because both neurons and astrocytes express IL-1 receptors, it cannot be determined if the electrophysiological consequences are driven by glial dependent or independent mechanisms, a caveat that is worth considering for many of the studies examined here. Regardless, inhibition of IL-1 signaling in the basolateral amygdala via local infusions of IL-1 receptor antagonist reduced acquisition of alcohol, suggesting that cytokine expression in the amygdala could modulate the reinforcing effects of alcohol (Marshall et al, 2016).…”

Section: Alcohol Glia and Neuroimmune Signalingmentioning

confidence: 99%

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

212

170

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Drugs of abuse cause persistent alterations in synaptic plasticity that may underlie addiction behaviors. Evidence suggests glial cells have an essential and underappreciated role in the development and maintenance of drug abuse by influencing neuronal and synaptic functions in multifaceted ways. Microglia and astrocytes perform critical functions in synapse formation and refinement in the developing brain, and there is growing evidence that disruptions in glial function may be implicated in numerous neurological disorders throughout the lifespan. Linking evidence of function in health and under pathological conditions, this review will outline the glial and neuroimmune mechanisms that may contribute to drug-abuse liability, exploring evidence from opioids, alcohol, and psychostimulants. Drugs of abuse can activate microglia and astrocytes through signaling at innate immune receptors, which in turn influence neuronal function not only through secretion of soluble factors (eg, cytokines and chemokines) but also potentially through direct remodeling of the synapses. In sum, this review will argue that neural-glial interactions represent an important avenue for advancing our understanding of substance abuse disorders.

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“…However, reducing endotoxin release with antibiotics, probiotics, and drugs resulted in a loss of the stress hormone response, suggesting stress‐induced changes in blood endotoxin contribute to stress hormone responses (Ait‐Belgnaoui et al., 2012). Innate immune signaling cytokines also alter EtOH consumption (Marshall et al., 2016, 2017), and the cytokine receptors IL1R1 and TNFR1 contribute to stress‐induced EtOH consumption (Karlsson et al., 2017), suggesting the neuroimmune system may contribute to addiction. Cytokines also enhance stressful emotional states following alcohol withdrawal (Breese et al., 2008).…”

mentioning

confidence: 99%

Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects

Walter

Vetreno

Crews

2017

Alcoholism Clin & Exp Res

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BackgroundCycles of alcohol and stress are hypothesized to contribute to alcohol use disorders. How this occurs is poorly understood, although both alcohol and stress activate the neuroimmune system—the immune molecules and cells that interact with the nervous system. The effects of alcohol and stress on the neuroimmune system are mediated in part by peripheral signaling molecules. Alcohol and stress both enhance immunomodulatory molecules such as corticosterone and endotoxin to impact neuroimmune cells, such as microglia, and may subsequently impact neurons. In this study, we therefore examined the effects of acute and chronic ethanol (EtOH) on the corticosterone, endotoxin, and microglial and neuronal response to acute stress.MethodsMale Wistar rats were treated intragastrically with acute EtOH and acutely stressed with restraint/water immersion. Another group of rats was treated intragastrically with chronic intermittent EtOH and acutely stressed following prolonged abstinence. Plasma corticosterone and endotoxin were measured, and immunohistochemical stains for the microglial marker CD11b and neuronal activation marker c‐Fos were performed.ResultsAcute EtOH and acute stress interacted to increase plasma endotoxin and microglial CD11b, but not plasma corticosterone or neuronal c‐Fos. Chronic EtOH caused a lasting sensitization of stress‐induced plasma endotoxin, but not plasma corticosterone. Chronic EtOH also caused a lasting sensitization of stress‐induced microglial CD11b, but not neuronal c‐Fos.ConclusionsThese results find acute EtOH combined with acute stress enhanced plasma endotoxin, as well as microglial CD11b in many brain regions. Chronic EtOH followed by acute stress also increased plasma endotoxin and microglial CD11b, suggesting a lasting sensitization to acute stress. Overall, these data suggest alcohol and stress interact to increase plasma endotoxin, resulting in enhanced microglial activation that could contribute to disease progression.

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IL-1 receptor signaling in the basolateral amygdala modulates binge-like ethanol consumption in male C57BL/6J mice

Cited by 61 publications

References 61 publications

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects

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