Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    One in 12 adults suffer with alcohol use disorder (AUD). Studies suggest the younger the age in which alcohol consumption begins the higher the probability of being diagnosed with AUD. Binge/excessive alcohol drinking involves a transition from flexible to inflexible behavior likely involving the dorsal striatum (caudate and putamen nuclei). A major focus of this study was to examine the effect of age of drinking onset on subsequent chronic, voluntary ethanol intake and dorsal striatal circuitry. Data from rhesus monkeys (n = 45) that started drinking as adolescents, young adults or mature adults confirms an age-related risk for heavy drinking. Striatal neuroadaptations were examined using whole-cell patch clamp electrophysiology to record AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABAA receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) from medium-sized spiny projection neurons located in the caudate or putamen nuclei. In controls, greater GABAergic transmission (mIPSC frequency and amplitude) was observed in the putamen compared to the caudate. With advancing age, in the absence of ethanol, an increase in mIPSC frequency concomitant with changes in mIPSC amplitude was observed in both regions. Chronic ethanol drinking decreased mIPSC frequency in the putamen regardless of age of onset. In the caudate, an ethanol drinking-induced increase in mIPSC frequency was only observed in monkeys that began drinking as young adults. Glutamatergic transmission did not differ between the dorsal striatal subregions in controls. With chronic ethanol drinking there was a decrease in the postsynaptic characteristics of rise time and area of mEPSCs in the putamen but an increase in mEPSC frequency in the caudate. Together, the observed changes in striatal physiology indicate a combined disinhibition due to youth and ethanol leading to abnormally strong activation of the putamen that could contribute to the increased risk for problem drinking in younger drinkers.

    Original languageEnglish (US)
    Pages (from-to)128-142
    Number of pages15
    JournalNeuropharmacology
    Volume131
    DOIs
    StatePublished - Mar 15 2018

    Fingerprint

    Inhibitory Postsynaptic Potentials
    Macaca mulatta
    Age of Onset
    Putamen
    Drinking
    Ethanol
    Corpus Striatum
    Excitatory Postsynaptic Potentials
    Caudate Nucleus
    Alcohol Drinking
    Young Adult
    Alcohols
    AMPA Receptors
    Electrophysiology
    GABA-A Receptors
    Haplorhini
    Neurons

    Keywords

    • Adolescent drinking
    • Adult drinking
    • Caudate
    • Non-human primate
    • Putamen
    • Whole-cell patch clamp electrophysiology

    ASJC Scopus subject areas

    • Pharmacology
    • Cellular and Molecular Neuroscience

    Cite this

    @article{6ee56beb77284420b2ad05e6c8c6549e,
    title = "Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset",
    abstract = "One in 12 adults suffer with alcohol use disorder (AUD). Studies suggest the younger the age in which alcohol consumption begins the higher the probability of being diagnosed with AUD. Binge/excessive alcohol drinking involves a transition from flexible to inflexible behavior likely involving the dorsal striatum (caudate and putamen nuclei). A major focus of this study was to examine the effect of age of drinking onset on subsequent chronic, voluntary ethanol intake and dorsal striatal circuitry. Data from rhesus monkeys (n = 45) that started drinking as adolescents, young adults or mature adults confirms an age-related risk for heavy drinking. Striatal neuroadaptations were examined using whole-cell patch clamp electrophysiology to record AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABAA receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) from medium-sized spiny projection neurons located in the caudate or putamen nuclei. In controls, greater GABAergic transmission (mIPSC frequency and amplitude) was observed in the putamen compared to the caudate. With advancing age, in the absence of ethanol, an increase in mIPSC frequency concomitant with changes in mIPSC amplitude was observed in both regions. Chronic ethanol drinking decreased mIPSC frequency in the putamen regardless of age of onset. In the caudate, an ethanol drinking-induced increase in mIPSC frequency was only observed in monkeys that began drinking as young adults. Glutamatergic transmission did not differ between the dorsal striatal subregions in controls. With chronic ethanol drinking there was a decrease in the postsynaptic characteristics of rise time and area of mEPSCs in the putamen but an increase in mEPSC frequency in the caudate. Together, the observed changes in striatal physiology indicate a combined disinhibition due to youth and ethanol leading to abnormally strong activation of the putamen that could contribute to the increased risk for problem drinking in younger drinkers.",
    keywords = "Adolescent drinking, Adult drinking, Caudate, Non-human primate, Putamen, Whole-cell patch clamp electrophysiology",
    author = "{Cuzon Carlson}, Verginia and Grant, {Kathleen (Kathy)} and Lovinger, {David M.}",
    year = "2018",
    month = "3",
    day = "15",
    doi = "10.1016/j.neuropharm.2017.12.010",
    language = "English (US)",
    volume = "131",
    pages = "128--142",
    journal = "Neuropharmacology",
    issn = "0028-3908",
    publisher = "Elsevier Limited",

    }

    TY - JOUR

    T1 - Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset

    AU - Cuzon Carlson, Verginia

    AU - Grant, Kathleen (Kathy)

    AU - Lovinger, David M.

    PY - 2018/3/15

    Y1 - 2018/3/15

    N2 - One in 12 adults suffer with alcohol use disorder (AUD). Studies suggest the younger the age in which alcohol consumption begins the higher the probability of being diagnosed with AUD. Binge/excessive alcohol drinking involves a transition from flexible to inflexible behavior likely involving the dorsal striatum (caudate and putamen nuclei). A major focus of this study was to examine the effect of age of drinking onset on subsequent chronic, voluntary ethanol intake and dorsal striatal circuitry. Data from rhesus monkeys (n = 45) that started drinking as adolescents, young adults or mature adults confirms an age-related risk for heavy drinking. Striatal neuroadaptations were examined using whole-cell patch clamp electrophysiology to record AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABAA receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) from medium-sized spiny projection neurons located in the caudate or putamen nuclei. In controls, greater GABAergic transmission (mIPSC frequency and amplitude) was observed in the putamen compared to the caudate. With advancing age, in the absence of ethanol, an increase in mIPSC frequency concomitant with changes in mIPSC amplitude was observed in both regions. Chronic ethanol drinking decreased mIPSC frequency in the putamen regardless of age of onset. In the caudate, an ethanol drinking-induced increase in mIPSC frequency was only observed in monkeys that began drinking as young adults. Glutamatergic transmission did not differ between the dorsal striatal subregions in controls. With chronic ethanol drinking there was a decrease in the postsynaptic characteristics of rise time and area of mEPSCs in the putamen but an increase in mEPSC frequency in the caudate. Together, the observed changes in striatal physiology indicate a combined disinhibition due to youth and ethanol leading to abnormally strong activation of the putamen that could contribute to the increased risk for problem drinking in younger drinkers.

    AB - One in 12 adults suffer with alcohol use disorder (AUD). Studies suggest the younger the age in which alcohol consumption begins the higher the probability of being diagnosed with AUD. Binge/excessive alcohol drinking involves a transition from flexible to inflexible behavior likely involving the dorsal striatum (caudate and putamen nuclei). A major focus of this study was to examine the effect of age of drinking onset on subsequent chronic, voluntary ethanol intake and dorsal striatal circuitry. Data from rhesus monkeys (n = 45) that started drinking as adolescents, young adults or mature adults confirms an age-related risk for heavy drinking. Striatal neuroadaptations were examined using whole-cell patch clamp electrophysiology to record AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABAA receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) from medium-sized spiny projection neurons located in the caudate or putamen nuclei. In controls, greater GABAergic transmission (mIPSC frequency and amplitude) was observed in the putamen compared to the caudate. With advancing age, in the absence of ethanol, an increase in mIPSC frequency concomitant with changes in mIPSC amplitude was observed in both regions. Chronic ethanol drinking decreased mIPSC frequency in the putamen regardless of age of onset. In the caudate, an ethanol drinking-induced increase in mIPSC frequency was only observed in monkeys that began drinking as young adults. Glutamatergic transmission did not differ between the dorsal striatal subregions in controls. With chronic ethanol drinking there was a decrease in the postsynaptic characteristics of rise time and area of mEPSCs in the putamen but an increase in mEPSC frequency in the caudate. Together, the observed changes in striatal physiology indicate a combined disinhibition due to youth and ethanol leading to abnormally strong activation of the putamen that could contribute to the increased risk for problem drinking in younger drinkers.

    KW - Adolescent drinking

    KW - Adult drinking

    KW - Caudate

    KW - Non-human primate

    KW - Putamen

    KW - Whole-cell patch clamp electrophysiology

    UR - http://www.scopus.com/inward/record.url?scp=85038845361&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85038845361&partnerID=8YFLogxK

    U2 - 10.1016/j.neuropharm.2017.12.010

    DO - 10.1016/j.neuropharm.2017.12.010

    M3 - Article

    C2 - 29241653

    AN - SCOPUS:85038845361

    VL - 131

    SP - 128

    EP - 142

    JO - Neuropharmacology

    JF - Neuropharmacology

    SN - 0028-3908

    ER -