Lentiviral Vector-Mediated dopamine D3 receptor modulation in the rat brain impairs alcohol intake and ethanol-induced conditioned place preference

Amine Bahi, Jean Luc Dreyer

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background: It has been reported that dopamine D3 receptor (D3R) knockout mice display similar ethanol (EtOH) consumption compared to wild types. In addition, studies with D3R pharmacological targeting were inconclusive. Methods: In the current study, we used both gain- and loss-of-function approaches to test the effects of central D3R manipulation on voluntary alcohol intake and EtOH-induced conditioned place preference (CPP) in rats. To this aim, we developed a lentiviral-mediated gene transfer approach to examine whether D3R knockdown (LV-siD3R) or overexpression (LV-D3R) in the nucleus accumbens (NAcc) is sufficient to modulate voluntary alcohol consumption and EtOH-CPP. Results: Using the standard 2-bottle choice drinking paradigm and an unbiased CPP procedure, our results indicated that, like the D3R selective antagonist SB-277011-A, LV-siD3R attenuated voluntary alcohol consumption. In contrast, LV-D3R increased EtOH intake with no effect on total fluid intake. Similarly, the D3R agonist 7-OH-DPAT also exacerbated EtOH intake. Interestingly, neither pharmacological nor genetic manipulation of D3R activity affected saccharin and quinine consumption and preference. More importantly, we report that LV-siD3R blocked, whereas LV-D3R exacerbated, EtOH-CPP. Conclusions: These results support the notion that the D3R plays an important role in alcohol reward in rats and suggest that a key threshold range of D3R levels is associated with impaired alcohol consumption. Taken together, these findings demonstrate that the D3R is an essential component of the molecular pathways underlying the reinforcing properties of alcohol. Thus, medications targeting the D3Rs may be beneficial to tackle EtOH abuse and alcoholism in humans.

Original languageEnglish
Pages (from-to)2369-2376
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume38
Issue number9
DOIs
Publication statusPublished - 2014

Keywords

  • Alcoholism
  • Conditioned place preference
  • Gene therapy
  • Lentivirus
  • SiRNA
  • Two-bottle choice

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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