Involvement of nucleus accumbens dopamine D1 receptors in ethanol drinking, ethanol-induced conditioned place preference, and ethanol-induced psychomotor sensitization in mice.
BACKGROUND
Dopamine D1 receptor (D1R) signaling has been associated to ethanol consumption and reward in laboratory animals.


OBJECTIVE
Here, we hypothesize that this receptor, which is located within the nucleus accumbens (NAc) neurons, modulates alcohol reward mechanisms.


METHODS
To test this hypothesis, we measured alcohol consumption and ethanol-induced psychomotor sensitization and conditioned place preference (CPP) in mice that received bilateral microinjections of small interference RNA (siRNA)-expressing lentiviral vectors (LV-siD1R) producing D1R knock-down. The other group received control (LV-Mock) viral vectors into the NAc.


RESULTS
There were no differences in the total fluid consumed and also no differences in the amount of ethanol consumed between groups prior to surgery. However, after surgery, the LV-siD1R group consumed less ethanol than the control group. This difference was not associated to taste neophobia. In addition, results have shown that down-regulation of endogenous D1R using viral-mediated siRNA in the NAc significantly decreased ethanol-induced behavioral sensitization as well as acquisition, but not expression, of ethanol-induced place preference.


CONCLUSIONS
We conclude that decreased D1R expression into the NAc led to reduced ethanol rewarding properties, thereby leading to lower voluntary ethanol consumption. Together, these findings demonstrate that the D1 receptor pathway within the NAc controls ethanol reward and intake.
Department of Anatomy, Faculty of Medicine & Health Sciences, United Arab Emirates University, Tawam Medical Campus, PO Box 17666, Al Ain, United Arab Emirates. amine.bahi@uaeu.ac.ae
Amine
A
Bahi
Jean-Luc
JL
Dreyer
D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009474:Neurons / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D012201:Reward
D034741:RNA, Small Interfering; D017447:Receptors, Dopamine D1; D000431:Ethanol