This article is a US government work and, as such, is in the public domain in the United States of America.
D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats†
Version of Record online: 16 APR 2008
Published 2008 Wiley-Liss, Inc.
Volume 62, Issue 7, pages 481–486, July 2008
How to Cite
Thanos, P. K., Michaelides, M., Umegaki, H. and Volkow, N. D. (2008), D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats. Synapse, 62: 481–486. doi: 10.1002/syn.20523
- Issue online: 24 APR 2008
- Version of Record online: 16 APR 2008
- Manuscript Accepted: 21 JAN 2008
- Manuscript Received: 9 OCT 2007
- NIAAA Intramural Research Program. Grant Numbers: AA11034, AA07574, AA07611
- U.S. Department of Energy. Grant Number: DE-AC02-98CH10886
- drug abuse;
- gene therapy;
Dopamine (DA) D2 receptor (D2R) agonists and antagonists can modulate self-administration behavior, conditioned place preference, and locomotor responses to cocaine. Low levels of D2R have also been observed in cocaine addicted subjects and in non human primates after chronic cocaine exposures. Prior studies had shown that D2R upregulation in the nucleus accumbens (NAc) in rodents trained to self-administer alcohol markedly attenuated alcohol preference and intake. Here we assess the effects of D2R upregulation in the NAc on cocaine intake in rats trained to self-administer cocaine. Following 2 weeks of i.v. cocaine self-administration (CSA), rats were stereotaxically treated with an adenovirus that carried the D2R gene to upregulate D2R in the NAc. D2R vector treatment resulted in a significant decrease (75%) in cocaine infusions and lever presses (70%) for cocaine. This effect lasted 6 days before cocaine consumption returned to baseline levels, which corresponds roughly to the time it takes D2R to return to baseline levels. These findings show that CSA and D2R in the NAc are negatively correlated and suggest that cocaine intake is modulated in part by D2R levels in NAc. Thus strategies aimed at increasing D2R expression in NAc may be beneficial in treating cocaine abuse and addiction. Synapse 62:481–486, 2008. Published 2008 Wiley-Liss, Inc.