Overexpression of dopamine D2 receptors reduces alcohol self-administration

The mechanism(s) underlying predisposition to alcohol abuse are poorly unde rstood but may involve brain dopamine system(s). Here we used an adenoviral vector to deliver the dopamine D2 receptor (DRD2) gene into the nucleus ac cumbens of rats, previously trained to self-administer alcohol, and to asse ss if DRD2 levels regulated alcohol preference and intake. We show that inc reases in DRD2 (52%) were associated with marked reductions in alcohol pref erence (43%), and alcohol intake (64%) of ethanol preferring rats, which re covered as the DRD2, returned to baseline levels. In addition, this DRD2 ov erexpression similarly produced significant reductions in ethanol nonprefer ring rats, in both alcohol preference (16%) and alcohol intake (75%). This is the first evidence that overexpression of DRD2 reduces alcohol intake an d suggests that high levels of DRD2 may be protective against alcohol abuse .