Protracted alcohol abstinence induces analgesia in rats: Possible relationships with BDNF and interleukin-10

Schunck, Rebeca Vargas Antunes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Souza, Andressa de; Macedo, Isabel Cristina de; Valle, Marina Tuerlinckx Costa; Salomón, Janaína L.O.; Moreira, Sônia Fátima da Silva; Kuo, Jonnsin; Arbo, Marcelo Dutra; Dallegrave, Eliane; Leal, Mirna Bainy

doi:10.1016/j.pbb.2015.05.011

Cited by 22 publications

(27 citation statements)

References 49 publications

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“…This was accompanied by an increase in interleukin-10 (IL-10), an antiinflammatory cytokine, as well as an increase in the nociceptive threshold, measured in the tail flick and hot plate tests (Schunck et al, 2015). This is consistent with the observation that BDNF infusions in different brain regions or in spinal cord may produce analgesia.…”

Section: Increase In Bdnf Levelssupporting

confidence: 83%

BDNF During Withdrawal

Geoffroy¹,

Noble²

2017

Vitamins and Hormones

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Section: Increase In Bdnf Levelssupporting

confidence: 83%

BDNF During Withdrawal

Geoffroy¹,

Noble²

2017

Vitamins and Hormones

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“…Since IL-10 is a cytokine with anti-inflammatory and neuroprotective properties, this observation suggests early adaptive neuroprotective changes after an acute EtOH exposure. Interestingly, other studies report protracted elevations in IL-10 peptide levels 7 days after a 4-day binge EtOH exposure, without a breach in the BBB, as well as after 12-day withdrawal in a chronic EtOH exposure model (Marshall et al, 2013; Schunck et al, 2015). Moreover, it has been shown that IL-10 cannot cross the BBB (Kastin et al, 2003).…”

Section: Discussionmentioning

confidence: 97%

Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol

et al. 2016

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Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic EtOH exposure. In the present study, we show that IL-10 is increased early (1 h) after a single intoxicating dose of EtOH (5 g/kg, intragastric) in Sprague Dawley rats. We also show that IL-10 rapidly regulates GABAergic transmission in dentate gyrus neurons. In brain slice recordings, IL-10 application dose-dependently decreases miniature inhibitory postsynaptic current (mIPSC) area and frequency, and decreases the magnitude of the picrotoxin sensitive tonic current (Itonic), indicating both pre- and postsynaptic mechanisms. A PI3K inhibitor LY294002 (but not the negative control LY303511) ablated the inhibitory effects of IL-10 on mIPSC area and Itonic, but not on mIPSC frequency, indicating the involvement of PI3K in postsynaptic effects of IL-10 on GABAergic transmission. Lastly, we also identify a novel neurobehavioral regulation of EtOH sensitivity by IL-10, whereby IL-10 attenuates acute EtOH-induced hypnosis. These results suggest that EtOH causes an early release of IL-10 in the brain, which may contribute to neuronal hyperexcitability as well as disturbed sleep seen after binge exposure to EtOH. These results also identify IL-10 signaling as a potential therapeutic target in alcohol-use disorders and other CNS disorders where GABAergic transmission is altered.

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“…Moreover, IHC analyses suggest that the focal point of IL-10 immunoreactivity depression was the BLA and not the CeA. Whether IL-10 immunoreactivity depression persists in abstinence is still to be determined, but other AUD models suggest that this effect is transient as protracted alcohol abstinence results in upregulation of IL-10 (Marshall et al 2013; Schunck et al 2015; Suryanarayanan et al 2016). Most importantly, this data indicates that excessive ethanol consumption elicits a neuroimmune response independent of, and prior to, peripheral immune system dysregulation observed in clinical studies of alcoholics (McClain and Cohen 1989; Nikou et al 2016; O’Halloran et al 2016).…”

Section: Discussionmentioning

confidence: 99%

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.

show abstract

Protracted alcohol abstinence induces analgesia in rats: Possible relationships with BDNF and interleukin-10

Cited by 22 publications

References 49 publications

BDNF During Withdrawal

BDNF During Withdrawal

Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol

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

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