Overexpression of dopamine D2 receptors reduces alcohol self-administration
Article first published online: 20 DEC 2001
Journal of Neurochemistry
Volume 78, Issue 5, pages 1094–1103, September 2001
How to Cite
Thanos, P. K., Volkow, N. D., Freimuth, P., Umegaki, H., Ikari, H., Roth, G., Ingram, D. K. and Hitzemann, R. (2001), Overexpression of dopamine D2 receptors reduces alcohol self-administration. Journal of Neurochemistry, 78: 1094–1103. doi: 10.1046/j.1471-4159.2001.00492.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received April 3, 2001; revised manuscript received June 13, 2001; accepted June 14, 2001.
- animal model;
- drinking preference;
- gene therapy;
- nucleus accumbens
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.