Contribution of NMDA glutamate and nicotinic acetylcholine receptor mechanisms in the discrimination of ethanolnicotine mixtures

Matthew Ford, Natalie L. Davis, Aubrey D. McCracken, Kathleen (Kathy) Grant

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Ethanol and nicotine are commonly coabused drugs, and the incidence of codependence is greater than would be expected on the basis of the summed probability of dependence on each drug alone. Previous findings from our laboratory and others suggest that interactive mechanisms at the level of discriminative stimulus (SD) effects may contribute to this coabuse phenomenon. Specifically, ethanol overshadows the nicotine SD whereas nicotine potentiates the stimulus salience of ethanol when the two drugs are conditioned as a drug mixture. The goal of the current study was to begin to delineate the pharmacological bases of these ethanolnicotine interactions. Three groups of C57BL/6J mice were trained to discriminate 0.8 mg/kg nicotine + 0.5 g/kg ethanol (0.8N + 0.5E), 0.8N + 1.0E, or 0.8N + 2.0E. An NMDA receptor antagonist (MK-801) and three nACh receptor ligands were tested for their ability to generalize from or antagonize, respectively, the drug mixtures. MK-801 fully generalized from the 0.8N + 1.0E and 0.8N +2.0E mixtures and partially generalized from 0.8N + 0.5E. In contrast, nACh receptor ligands had minimal influence in blocking the perception of 0.8N + 1.0E and 0.8N + 2.0E mixtures, and only mecamylamine partially blocked 0.8N +0.5E. Reduced and enhanced contributions of nACh and NMDA receptors, respectively, in the discrimination of ethanol nicotine mixtures may contribute to the overshadowing and potentiation phenomena observed previously. Behavioural Pharmacology 24:617622

    Original languageEnglish (US)
    Pages (from-to)617-622
    Number of pages6
    JournalBehavioural Pharmacology
    Volume24
    Issue number7
    DOIs
    StatePublished - Oct 2013

    Fingerprint

    Nicotinic Receptors
    N-Methylaspartate
    Nicotine
    Glutamic Acid
    Ethanol
    Pharmaceutical Preparations
    Dizocilpine Maleate
    N-Methyl-D-Aspartate Receptors
    Pharmacology
    Ligands
    Mecamylamine
    Aptitude
    Inbred C57BL Mouse
    Discrimination (Psychology)
    Incidence

    Keywords

    • Antagonism
    • Drug discrimination
    • Drug mixture
    • Ethanol
    • Mouse
    • NACh receptor
    • Nicotine
    • NMDA receptor
    • Overshadowing
    • Substitution

    ASJC Scopus subject areas

    • Pharmacology
    • Psychiatry and Mental health

    Cite this

    Contribution of NMDA glutamate and nicotinic acetylcholine receptor mechanisms in the discrimination of ethanolnicotine mixtures. / Ford, Matthew; Davis, Natalie L.; McCracken, Aubrey D.; Grant, Kathleen (Kathy).

    In: Behavioural Pharmacology, Vol. 24, No. 7, 10.2013, p. 617-622.

    Research output: Contribution to journalArticle

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    abstract = "Ethanol and nicotine are commonly coabused drugs, and the incidence of codependence is greater than would be expected on the basis of the summed probability of dependence on each drug alone. Previous findings from our laboratory and others suggest that interactive mechanisms at the level of discriminative stimulus (SD) effects may contribute to this coabuse phenomenon. Specifically, ethanol overshadows the nicotine SD whereas nicotine potentiates the stimulus salience of ethanol when the two drugs are conditioned as a drug mixture. The goal of the current study was to begin to delineate the pharmacological bases of these ethanolnicotine interactions. Three groups of C57BL/6J mice were trained to discriminate 0.8 mg/kg nicotine + 0.5 g/kg ethanol (0.8N + 0.5E), 0.8N + 1.0E, or 0.8N + 2.0E. An NMDA receptor antagonist (MK-801) and three nACh receptor ligands were tested for their ability to generalize from or antagonize, respectively, the drug mixtures. MK-801 fully generalized from the 0.8N + 1.0E and 0.8N +2.0E mixtures and partially generalized from 0.8N + 0.5E. In contrast, nACh receptor ligands had minimal influence in blocking the perception of 0.8N + 1.0E and 0.8N + 2.0E mixtures, and only mecamylamine partially blocked 0.8N +0.5E. Reduced and enhanced contributions of nACh and NMDA receptors, respectively, in the discrimination of ethanol nicotine mixtures may contribute to the overshadowing and potentiation phenomena observed previously. Behavioural Pharmacology 24:617622",
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