The effect of dopamine D4 receptor density on novelty seeking, activity, social interaction, and alcohol binge drinking in adult mice.
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.
Department of Psychology, Behavioral Neuropharmacology and Neuroimaging Lab, Stony Brook University, Stony Brook, New York.
Panayotis K
PK
Thanos
Department of Psychology, Behavioral Neuropharmacology and Neuroimaging Lab, Stony Brook University, Stony Brook, New York.
Kareema
K
Roushdy
Department of Psychology, Behavioral Neuropharmacology and Neuroimaging Lab, Stony Brook University, Stony Brook, New York.
Zehan
Z
Sarwar
Department of Psychology, Furman University, Greenville, South Carolina.
Onarae
O
Rice
Department of Pharmaceutical Sciences, St. Johns University, Queens, New York.
Charles R
CR
Ashby
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon.|Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon.
David K
DK
Grandy
D000428:Alcohol Drinking / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D063425:Binge Drinking / Q000235:genetics*; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors
C493600:Drd4 protein, mouse; D050638:Receptors, Dopamine D4
D4 receptor; Drd4; addiction; alcohol abuse; anxiety; ethanol; locomotor activity; novelty seeking; social interaction