The effect of dopamine D4 receptor density on novelty seeking, activity, social interaction, and alcohol binge drinking in adult mice

Panayotis K. Thanos, Kareema Roushdy, Zehan Sarwar, Onarae Rice, Charles R. Ashby, David K. Grandy

    Research output: Contribution to journalArticle

    8 Scopus citations

    Abstract

    The dopamine D4 receptor has been postulated to play a role in the pathophysiology of alcoholism. This study examined how varying levels of D4 expression and their associated behaviors in male and female mice correlate with future alcohol intake. We hypothesized that: (1) mice with low (Drd4+/-) or deficient (Drd4-/-) in D4 receptors would show enhanced ethanol consumption compared with control mice (Drd4+/+), and (2) a specific phenotype in these mice is associated with future vulnerability for alcohol consumption. Individually housed mice were allowed free access to ethanol (20% vv) in the dark (DID). The behaviors measured in male and female mice were: novel object recognition, open-field locomotor activity, and social interaction. Correlation analyses showed that in male Drd4-/- mice (relative to Drd4+/+ controls), anxiolytic behavior was significantly correlated with increased alcohol consumption. Also, in male Drd4-/- mice, there was a significant positive correlation between increased exploratory behavior and increased alcohol consumption. These findings were not observed in females. In conclusion, our data suggest that the dopamine D4 receptor gene has an important role in increased exploratory and anxiolytic behavior only in males and these behaviors were positively correlated with increased alcohol consumption. This interaction between sex hormones and dopamine D4 receptor genotype/function predicting future alcohol abuse and correlation with anxiolytic and exploratory behavior in male mice could have important implications for better understanding of vulnerabilities associated with addiction.

    Original languageEnglish (US)
    Pages (from-to)356-364
    Number of pages9
    JournalSynapse
    Volume69
    Issue number7
    DOIs
    StatePublished - Jul 1 2015

    Keywords

    • Addiction
    • Alcohol abuse
    • Anxiety
    • D4 receptor
    • Drd4
    • Ethanol
    • Locomotor activity
    • Novelty seeking
    • Social interaction

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

    Fingerprint Dive into the research topics of 'The effect of dopamine D4 receptor density on novelty seeking, activity, social interaction, and alcohol binge drinking in adult mice'. Together they form a unique fingerprint.

  • Cite this