Overexpression of dopamine D2 receptors reduces alcohol self‐administration

PK Thanos, ND Volkow, P Freimuth… - Journal of …, 2001 - Wiley Online Library
PK Thanos, ND Volkow, P Freimuth, H Umegaki, H Ikari, G Roth, DK Ingram, R Hitzemann
Journal of neurochemistry, 2001Wiley Online Library
The mechanism (s) underlying predisposition to alcohol abuse are poorly understood but
may involve brain dopamine system (s). Here we used an adenoviral vector to deliver the
dopamine D2 receptor (DRD2) gene into the nucleus accumbens of rats, previously trained
to self‐administer alcohol, and to assess if DRD2 levels regulated alcohol preference and
intake. We show that increases in DRD2 (52%) were associated with marked reductions in
alcohol preference (43%), and alcohol intake (64%) of ethanol preferring rats, which …
The mechanism(s) underlying predisposition to alcohol abuse are poorly understood but may involve brain dopamine system(s). Here we used an adenoviral vector to deliver the dopamine D2 receptor (DRD2) gene into the nucleus accumbens of rats, previously trained to self‐administer alcohol, and to assess if DRD2 levels regulated alcohol preference and intake. We show that increases in DRD2 (52%) were associated with marked reductions in alcohol preference (43%), and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. In addition, this DRD2 overexpression similarly produced significant reductions in ethanol non‐preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This is the first evidence that overexpression of DRD2 reduces alcohol intake and suggests that high levels of DRD2 may be protective against alcohol abuse.
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