Agmatine reduces alcohol drinking and produces antinociceptive effects in rodent models of alcohol use disorder

López, Marcelo F.; Davis, E. G.; Cucinello-Ragland, Jessica A.; Regunathan, S.; Edwards, Scott; Becker, Howard C.

doi:10.1016/j.alcohol.2023.01.003

Cited by 5 publications

(2 citation statements)

References 50 publications

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“…To date, the majority of AWH studies performed in mice have utilized a range of ethanol exposure models, such as chronic intermittent ethanol vapor (CIE), intermittent access two‐bottle choice (IA2BC), and drinking in the dark (DID) (Bergeson et al., 2016; Lopez et al., 2023; Morgan et al., 2022; Okhuarobo et al., 2020, 2023; Quadir, Tanino, Rohl, et al., 2021; Quadir, Tanino, Sami, et al., 2021; Smith et al., 2016, 2017; Tonetto et al., 2023). However, to the best of our knowledge, no one has reported AWH in mice using the Lieber–DeCarli model.…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitor decreases hyperalgesia in a mouse model of alcohol withdrawal‐induced hyperalgesia

Aguilar,

De Carvalho,

Chen

et al. 2024

Alcohol, Clinical and Experimental Research

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BackgroundAlcohol withdrawal‐induced hyperalgesia (AWH) is characterized as an increased pain sensitivity observed after cessation of chronic alcohol use. Alcohol withdrawal‐induced hyperalgesia can contribute to the negative affective state associated with abstinence and can increase susceptibility to relapse. We aimed to characterize pain sensitivity in mice during withdrawal from two different models of alcohol exposure: chronic drinking in the dark (DID) and the Lieber–DeCarli liquid diet. We also investigated whether treatment with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), could ameliorate AWH in mice treated with the Lieber–DeCarli diet.MethodsMale and female C57BL/6J mice were used for these studies. In the DID model, mice received bottles of 20% ethanol or water during the dark cycle for 4 h per day on four consecutive days per week for 6 weeks. Peripheral mechanical sensitivity was measured weekly the morning of Day 5 using von Frey filaments. In the Lieber–DeCarli model, mice received ethanol (5% v/v) or control liquid diet for 10 days, along with a single binge ethanol gavage (5 g/kg) or control gavage, respectively, on Day 10. Peripheral mechanical sensitivity was measured during the liquid diet administration and at 24 and 72 h into ethanol withdrawal. An independent group of mice that received the Lieber–DeCarli diet were administered SAHA (50 mg/kg, i.p.) during withdrawal.ResultsMale mice exhibited mechanical hypersensitivity after consuming ethanol for 5 weeks in the DID procedure. In the Lieber–DeCarli model, ethanol withdrawal led to hyperalgesia in both sexes. Suberoylanilide hydroxamic acid treatment during withdrawal from the ethanol liquid diet alleviated AWH.ConclusionsThese results demonstrate AWH in mice after chronic binge drinking in males and after Lieber–DeCarli liquid diet administration in both sexes. Like previous findings in rats, HDAC inhibition reduced AWH in mice, suggesting that epigenetic mechanisms are involved in AWH.

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Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitor decreases hyperalgesia in a mouse model of alcohol withdrawal‐induced hyperalgesia

Aguilar,

De Carvalho,

Chen

et al. 2024

Alcohol, Clinical and Experimental Research

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“…Agmatine, which is an endogenous neurotransmitter or neuromodulator (Reis & Regunathan, 2000) formed from the decarboxylation of L‐arginine amino acid (Aricioglu & Regunathan, 2005; Moretti et al., 2014; Piletz et al., 2013; Reis & Regunathan, 2000; Xu et al., 2018; Zhu et al., 2004) modulates GC‐mediated stress effects and has therefore been identified as a potential pharmacotherapy for stress (Zhu et al., 2008). In addition, agmatine has demonstrated therapeutic potential in the treatment of dependence on alcohol and opiates (Piletz et al., 2013; Lopez et al., 2023). As a neuromodulator, agmatine acts on several targets on the cell membrane, including N ‐methyl‐ d ‐aspartate (NMDA) receptors, α‐2 adrenergic receptors, and nitric oxide synthase (NOS) (Piletz et al., 1995; Galea et al., 1996; Reis & Regunathan, 2000; Berkels et al., 2004; Halaris & Plietz, 2007; Taksande et al., 2009; Uzbay, 2012; Neis et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

Preventive putative effect of agmatine on cognitive and molecular outcomes in ventral tegmental area of male offspring following physical and psychological prenatal stress

Hassanshahi

Janahmadi

Razavinasab

et al. 2023

Developmental Psychobiology

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Prenatal stress (PS) results from a maternal experience of stressful events during pregnancy, which has been associated with an increased risk of behavioral disorders including substance abuse and anxiety in the offspring. PS is known to result in heightened dopamine release in the ventral tegmental area (VTA), in part through the effects of corticotropin‐releasing hormone, which directly excites dopaminergic cells. It has recently been suggested that agmatine plays a role in modulating anxiety‐like behaviors. In this study, we investigated whether agmatine could reduce negative cognitive outcomes in male mice prenatally exposed to psychological/physical stress, and whether this could be associated with molecular changes in VTA. Agmatine (37.5 mg/kg) was administrated 30 min prior to PS induction in pregnant Swiss mice. Male offspring were evaluated in a series of behavioral and molecular assays. Findings demonstrated that agmatine reduced the impairment in locomotor activity induced by both psychological and physical PS. Agmatine also decreased heightened conditioned place preference to morphine seen in PS offspring. Moreover, agmatine ameliorated the anxiety‐like behavior and drug‐seeking behavior induced by PS in the male offspring. Molecular effects were seen in VTA as the enhanced brain‐derived neurotrophic factor (BDNF) induced by PS in the VTA was reduced by agmatine. Behavioral tests indicate that agmatine exerts a protective effect on PS‐induced impairments in male offspring, which could be due in part to agmatine‐associated molecular alterations in the VTA. Taken together, our data suggest that prenatal treatment with agmatine exerts protective effect against negative consequences of PS on the development of affective circuits in the offspring.

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Within and Beyond the Binary: Sex and Gender Differences in Pain and Alcohol Use Disorder

Fitzpatrick-Schmidt,

Edwards

2023

Curr Addict Rep

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Agmatine reduces alcohol drinking and produces antinociceptive effects in rodent models of alcohol use disorder

Cited by 5 publications

References 50 publications

Histone deacetylase inhibitor decreases hyperalgesia in a mouse model of alcohol withdrawal‐induced hyperalgesia

Histone deacetylase inhibitor decreases hyperalgesia in a mouse model of alcohol withdrawal‐induced hyperalgesia

Preventive putative effect of agmatine on cognitive and molecular outcomes in ventral tegmental area of male offspring following physical and psychological prenatal stress

Within and Beyond the Binary: Sex and Gender Differences in Pain and Alcohol Use Disorder

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