The α3β4 nicotinic acetylcholine receptor antagonist 18-Methoxycoronaridine decreases binge-like ethanol consumption in adult C57BL/6J mice

Miller, Carley N.; Ruggery, Colton; Kamens, Helen M.

doi:10.1016/j.alcohol.2018.11.006

Cited by 13 publications

(12 citation statements)

References 37 publications

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“…Ethanol intake appears to involve a variety of nAChR subtypes (Joslyn et al, 2008; Saccone et al, 2009; Taslim and Saeed Dar, 2011). α7 (Kamens et al, 2010a) and α3β4 nAChRs (Chatterjee et al, 2011; Miller et al, 2019) have both been implicated in ethanol intake, and receptors containing the α5 nAChR subunit are thought to be associated with the sedative effects of ethanol (Santos et al, 2013). Furthermore, the α4β2 nAChR subtype may be involved in alcohol intake due to its role in the brain’s reward system.…”

Section: Introductionmentioning

confidence: 99%

UFR2709, a Nicotinic Acetylcholine Receptor Antagonist, Decreases Ethanol Intake in Alcohol-Preferring Rats

et al. 2019

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Brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric acetylcholine-gated cation channels, have been suggested as molecular targets for the treatment of alcohol abuse and dependence. Here, we examined the effect of the competitive nAChR antagonist UFR2709 on the alcohol consumption of high-alcohol-drinking UChB rats. UChB rats were given free access to ethanol for 24-h periods in a two-bottle free choice paradigm and their ethanol and water intake were measured. The animals were i.p. injected daily for 17 days with a 10, 5, 2.5, or 1 mg/kg dose of UFR2709. Potential confounding motor effects of UFR2709 were assessed by examining the locomotor activity of animals administered the highest dose of UR2709 tested (10 mg/kg i.p.). UFR2709 reduced ethanol consumption and ethanol preference and increased water consumption in a dose-dependent manner. The most effective dose of UFR2709 was 2.5 mg/kg, which induced a 56% reduction in alcohol consumption. Administration of UFR2709 did not affect the weight or locomotor activity of the rats, suggesting that its effects on alcohol consumption and preference were mediated by specific nAChRs.

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Section: Introductionmentioning

confidence: 99%

UFR2709, a Nicotinic Acetylcholine Receptor Antagonist, Decreases Ethanol Intake in Alcohol-Preferring Rats

et al. 2019

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“…Prior work using alcoholpreferring rats has shown that 18-MC decreases ethanol consumption (Rezvani et al, 2016(Rezvani et al, , 1997. Consistent findings in C57BL/6J mice showed that a high dose (30 mg/kg) of 18-MC reduces binge-like ethanol consumption without altering tastant intake, metabolism, or ethanol-induced sedation (Miller et al, 2019). Other work has examined the effects of 18-MC on ethanol-induced locomotor stimulation and sensitization.…”

Section: α5α3β4 Nachrsmentioning

confidence: 79%

The role of nicotinic acetylcholine receptors in alcohol-related behaviors

Miller

Kamens

2020

Brain Research Bulletin

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Alcohol use disorder (AUD) causes an alarming economic and health burden in the United States. Unfortunately, this disease does not exist in isolation; AUD is highly comorbid with nicotine use. Results from both human and animal models demonstrate a genetic correlation between alcohol and nicotine behaviors. These data support the idea of shared genetic and neural mechanisms underlying these behaviors. Nicotine acts directly at nicotinic acetylcholine receptors (nAChR) to have its pharmacological effect. Interestingly, alcohol also acts both directly and indirectly at these receptors. Research utilizing genetically engineered rodents and pharmacological manipulations suggest a role for nAChR in several ethanol behaviors. The current manuscript collates this literature and discusses findings that implicate specific nAChR subunits in ethanol phenotypes. These data suggest future directions for targeting nAChR as novel therapeutics for AUD.

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“…For injections, ethanol (20% vol/vol; 200 proof; Koptec, King of Prussia, PA) and 18-MC [(-)-18-methoxycoronaridine hydrochloride; Orbiter Research, Champaign, IL] were diluted in physiological saline (0.9% NaCl; Baxter, Dearfield, IL) and administered into the intraperitoneal cavity. 18-MC doses and pretreatment times were based on published work (Glick, Maisonneuve, & Szumlinski, 2000; Miller et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

“…One promising drug that targets nAChR is 18-methoxycoronaridine (18-MC). 18-MC is an α3β4 nAChR antagonist that reduces ethanol intake in male and female rodents without altering ethanol metabolism, tastant consumption, or ethanol-induced sedation (Miller, Ruggery, & Kamens, 2019; Rezvani et al, 2016, 1997). These findings suggest that 18-MC may specifically reduce ethanol consumption and that further research on its therapeutic potential should be conducted.…”

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confidence: 99%

Reduced expression of ethanol sensitization by α3β4 nicotinic acetylcholine receptors in DBA/2J mice.

Miller¹,

Kamens²

2020

Experimental and Clinical Psychopharmacology

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Alcohol use disorder (AUD) is a leading cause of preventable death in the United States, however existing treatments are ineffective and produce aversive side effects such as nausea and fatigue. One potential therapeutic for AUD is the α3β4 nicotinic acetylcholine receptor (nAChR) antagonist 18-methoxycoronaridine (18-MC). Prior work has shown that 18-MC reduces ethanol consumption in rodent models. The present study sought to further examine the therapeutic potential of 18-MC by testing its effects on nonconsummatory behaviors. We examined 2 behavioral measures: ethanol-induced locomotor stimulation, which measures euphoric properties of the drug, and the expression of locomotor sensitization which models neuroadaptations in response to repeated exposure. We tested dose-dependent effects of 18-MC (0, 10, 20 and 30 mg/kg) administration on ethanol stimulation and locomotor sensitization in female and male DBA/2J mice. 18-MC had no effect on acute ethanol-induced stimulation, but the highest dose (30 mg/kg) significantly decreased the expression of locomotor sensitization. Our results support the involvement of α3β4 nAChR in the expression of ethanol-induced locomotor sensitization and suggest that 18-MC may be a therapeutic for AUD.

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The α3β4 nicotinic acetylcholine receptor antagonist 18-Methoxycoronaridine decreases binge-like ethanol consumption in adult C57BL/6J mice

Cited by 13 publications

References 37 publications

UFR2709, a Nicotinic Acetylcholine Receptor Antagonist, Decreases Ethanol Intake in Alcohol-Preferring Rats

UFR2709, a Nicotinic Acetylcholine Receptor Antagonist, Decreases Ethanol Intake in Alcohol-Preferring Rats

The role of nicotinic acetylcholine receptors in alcohol-related behaviors

Reduced expression of ethanol sensitization by α3β4 nicotinic acetylcholine receptors in DBA/2J mice.

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