Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking.
Dopamine (DA) signals are transmitted via specific receptors including the D2 receptors (D2R). Previous studies have shown that D2R upregulation in the nucleus accumbens (NAc) attenuated alcohol consumption. We hypothesized that upregulation of D2R in the NAc would significantly influence alcohol drinking. We tested this hypothesis by determining the effect that D2R upregulation has on alcohol intake in genetically altered mice lacking D2Rs. After a steady baseline of drinking behavior was established for all mice, a null vector or a genetically modified adenoviral vector containing the rat D2R cDNA was infused into the NAc of wild-type (Drd2+/+), heterozygous (Drd2+/-), and receptor-deficient mice (Drd2-/-). Ethanol intake and preference were then determined using the two-bottle choice paradigm. Our results indicated that Drd2+/+ mice treated with the D2R vector significantly attenuated (58 %) their ethanol intake as well as reduced preference. Drd2+/- and mutant mice showed a similar attenuation, although the change was not as marked (12 %) and did not last as long. In contrast, Drd2-/- mice treated with the D2R vector displayed a temporary but significant increase (46 %) in ethanol intake and preference (consumption). These results supported the notion that the D2R plays an important role in alcohol consumption in mice and suggest that a key threshold range of D2R levels is associated with elevated alcohol consumption. Significant deviations in D2R levels from this range could impact alcohol consumption, and could help to explain possible individual variations in alcohol response, metabolism, sensitivity and consumption.
Thanos
Panayotis K
PK
Department of Medicine, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. thanos@bnl.gov
Rivera
Seth N
SN
Weaver
Katrina
K
Grandy
David K
DK
Rubinstein
Marcelo
M
Umegaki
Hiroyuki
H
Wang
Gene Jack
GJ
Hitzemann
Robert
R
Volkow
Nora D
ND
D000428:Alcohol Drinking; D000818:Animals; D003213:Conditioning, Psychological; D022761:Gene Transfer, Horizontal; D015316:Genetic Therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology
D017448:Receptors, Dopamine D2