Reduced Expression of Ethanol Sensitization by a3ß4 Nicotinic Acetylcholine Receptors in DBA/2J Mice

Carley N. Miller, Helen M. Kamens

    Research output: Contribution to journalArticle

    Abstract

    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.

    Original languageEnglish (US)
    JournalExperimental and clinical psychopharmacology
    DOIs
    StateAccepted/In press - Jan 1 2019

    Fingerprint

    Inbred DBA Mouse
    Nicotinic Receptors
    Ethanol
    Alcohols
    Therapeutic Uses
    Cholinergic Antagonists
    Nausea
    Fatigue
    18-methoxycoronaridine
    Cause of Death
    Rodentia
    Pharmaceutical Preparations

    All Science Journal Classification (ASJC) codes

    • Pharmacology
    • Psychiatry and Mental health
    • Pharmacology (medical)

    Cite this

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    abstract = "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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