The galanin-3 receptor antagonist, SNAP 37889, suppresses alcohol drinking and morphine self-administration in mice

Galanin is a neuropeptide which mediates its effects via three G-protein coupled receptors (GAL ). Administration of a GAL antagonist reduces alcohol self-administration in animal models while allelic variation in the GAL gene has been associated with an increased risk of alcohol use disorders in diverse human populations. Based on the association of GAL with alcoholism, we sought to characterize drug-seeking behavior in GAL -deficient mice for the first time. In the two-bottle free choice paradigm, GAL -KO mice consistently showed a significantly increased preference for ethanol over water when compared to wildtype littermates. Furthermore, male GAL -KO mice displayed significantly increased responding for ethanol under operant conditions. These differences in alcohol seeking behavior in GAL -KO mice did not result from altered ethanol metabolism. In contrast to ethanol, GAL -KO mice exhibited similar preference for saccharin and sucrose over water, and a similar preference for a high fat diet over a low fat diet as wildtype littermates. No differences in cognitive and locomotor behaviors were observed in GAL -KO mice to account for increased alcohol seeking behavior. Overall, these findings suggest genetic ablation of GAL in mice increases alcohol consumption.

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“…A similar study in mice yielded concurrent results (Scheller et al . ) which taken together, support a role of GAL 3 in alcohol dependence.…”

Section: Introductionsupporting

confidence: 55%

“…Similar results were also observed when SNAP 37889 was administered to mice during a scheduled high alcohol consumption paradigm (Scheller et al . ).…”

Section: Discussionmentioning

confidence: 97%

GAL₃ receptor knockout mice exhibit an alcohol‐preferring phenotype

et al. 2018

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“…; Scheller et al . ). Because GALR3 is mainly restricted to the hypothalamus and pituitary (Smith et al .…”

Section: Discussionmentioning

confidence: 97%

Central administration of galanin N‐terminal fragment 1–15 decreases the voluntary alcohol intake in rats

et al. 2017

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Alcohol consumption is considered a major risk factor for disease and mortality worldwide. In the absence of effective treatments in alcohol use disorders, it is important to find new biological targets that could modulate alcohol consumption. We tested the role of the N-terminal galanin fragment (1-15) [GAL(1-15)] in voluntary ethanol consumption in rats using the two-bottle choice paradigm as well as compare the effects of GAL(1-15) with the whole molecule of GAL. We describe for the first time that GAL(1-15), via central mechanisms, induces a strong reduction in preference and ethanol consumption in rats. These effects were significantly different than GAL. GAL receptor (GALR) 2 was involved in these effects, because the specific GALR2 antagonist M871 blocked GAL(1-15) mediated actions in preference and ethanol intake. Importantly, the mechanism of this action involves changes in GALR expression and also in immediate-early gene C-Fos and receptors-internalization-related gene Rab5 in the striatum. The relevance of the striatum as a target for GAL(1-15) was supported by the effect of GAL(1-15) on the locomotor activity of rats after ethanol administration. These results may give the basis for the development of novel therapeutics strategies using GAL(1-15) analogues for the treatment of alcohol use disorders in humans.

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“…Moreover, biophysical assays proved the direct interactions between these receptors and ZD, indicating that they were the direct functional targets of ZD (Figure ). In fact, modulation of specific receptors has proved to be a promising strategy in AFLD therapy, including the galanin‐3 receptor antagonist SNAP 37889, IL‐1 receptor antagonist anakinra, liver X receptor α antagonist 22‐S‐hydroxycholesterol, and PPARα agonist WY14643 …”

Section: Discussionmentioning

confidence: 99%

Wolfberry‐Derived Zeaxanthin Dipalmitate Attenuates Ethanol‐Induced Hepatic Damage

Gao

Liu

et al. 2019

Molecular Nutrition Food Res

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Scope: Besides abstinence and nutritional support, there is no proven clinical treatment for patients with alcoholic fatty liver disease (AFLD). Here, the therapeutic effects and mechanisms of action of wolfberry-derived zeaxanthin dipalmitate (ZD) on AFLD models are demonstrated. Methods and results: The hepatoprotective effects of ZD are evaluated in vitro and in vivo. Direct interacting receptors of ZD on cell membranes are identified by liver-specific knockdown and biophysical measurements. Downstream signaling pathways are delineated using molecular and cellular biological methods. It is demonstrated that ZD attenuates hepatocyte and whole-liver injury in ethanol-treated cells (dose: 1 µm) and a chronic binge AFLD rat model (dose: 10 mg kg -1 ), respectively. The direct targets of ZD on the cell membrane include receptor P2X7 and adiponectin receptor 1 (adipoR1).

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The galanin-3 receptor antagonist, SNAP 37889, suppresses alcohol drinking and morphine self-administration in mice

Cited by 16 publications

References 76 publications

GAL₃ receptor knockout mice exhibit an alcohol‐preferring phenotype

GAL₃ receptor knockout mice exhibit an alcohol‐preferring phenotype

Central administration of galanin N‐terminal fragment 1–15 decreases the voluntary alcohol intake in rats

Wolfberry‐Derived Zeaxanthin Dipalmitate Attenuates Ethanol‐Induced Hepatic Damage

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The galanin-3 receptor antagonist, SNAP 37889, suppresses alcohol drinking and morphine self-administration in mice

Cited by 16 publications

References 76 publications

GAL3 receptor knockout mice exhibit an alcohol‐preferring phenotype

GAL3 receptor knockout mice exhibit an alcohol‐preferring phenotype

Central administration of galanin N‐terminal fragment 1–15 decreases the voluntary alcohol intake in rats

Wolfberry‐Derived Zeaxanthin Dipalmitate Attenuates Ethanol‐Induced Hepatic Damage

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Product

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GAL₃ receptor knockout mice exhibit an alcohol‐preferring phenotype

GAL₃ receptor knockout mice exhibit an alcohol‐preferring phenotype