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 dr...

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Autor principal: Thanos, P.K
Otros Autores: Rivera, S.N, Weaver, K., Grandy, D.K, Rubinstein, M., Umegaki, H., Wang, G.J, Hitzemann, R., Volkow, N.D
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Elsevier Inc. 2005
Acceso en línea:Registro en Scopus
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100 1 |a Thanos, P.K. 
245 1 0 |a Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking 
260 |b Elsevier Inc.  |c 2005 
270 1 0 |m Thanos, P.K.; Department of Medicine, Brookhaven National Laboratory, Upton, NY 11973-5000, United States; email: thanos@bnl.gov 
506 |2 openaire  |e Política editorial 
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520 3 |a 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. © 2005 Elsevier Inc. All rights reserved.  |l eng 
536 |a Detalles de la financiación: U.S. Department of Energy, DE-AC02-98CH10886 
536 |a Detalles de la financiación: National Institute on Alcohol Abuse and Alcoholism, AA07611, AA 11034, AA07574 
536 |a Detalles de la financiación: National Institute of Mental Health, MH67497, MH66360 
536 |a Detalles de la financiación: National Institute of Development Administration, DA12062 
536 |a Detalles de la financiación: The authors thank, Katherine Suchland, Andrew Lee, Brittney Tejada, Maryann Kershaw and Dr. Bruce Scharf for assistance with this study and for veterinary care. We would also like to thank Brian Murfin, Kevin Manning and the SULI program at Brookhaven National Laboratory for supporting KW. This work was supported by the NIAAA (AA 11034 & AA07574, AA07611), NIMH (MH66360 & MH67497) and NIDA (DA12062) and by the U.S. Department of Energy under contract DE-AC02-98CH10886. 
593 |a Department of Medicine, Brookhaven National Laboratory, Upton, NY 11973-5000, United States 
593 |a Dept. of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97201, United States 
593 |a INGEBI (CONICET), Dept. Fisiol., Biol. Molec. Y Cel., University of Buenos Aires, 1428 Buenos Aires, Argentina 
593 |a Dept. of Geriatrics, Univ. of Nagoya, School of Medicine, Aichi 466-8550, Japan 
690 1 0 |a ADDICTION 
690 1 0 |a ALCOHOLISM 
690 1 0 |a ASSOCIATIVE LEARNING 
690 1 0 |a GENE THERAPY 
690 1 0 |a ADENOVIRUS VECTOR 
690 1 0 |a ALCOHOL 
690 1 0 |a COMPLEMENTARY DNA 
690 1 0 |a DNA 
690 1 0 |a DOPAMINE 2 RECEPTOR 
690 1 0 |a ALCOHOL CONSUMPTION 
690 1 0 |a ALCOHOL METABOLISM 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ARTICLE 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DNA MODIFICATION 
690 1 0 |a DNA TRANSFER 
690 1 0 |a DRINKING BEHAVIOR 
690 1 0 |a HETEROZYGOSITY 
690 1 0 |a MALE 
690 1 0 |a MOUSE 
690 1 0 |a NONHUMAN 
690 1 0 |a NUCLEUS ACCUMBENS 
690 1 0 |a RECEPTOR UPREGULATION 
690 1 0 |a WILD TYPE 
700 1 |a Rivera, S.N. 
700 1 |a Weaver, K. 
700 1 |a Grandy, D.K. 
700 1 |a Rubinstein, M. 
700 1 |a Umegaki, H. 
700 1 |a Wang, G.J. 
700 1 |a Hitzemann, R. 
700 1 |a Volkow, N.D. 
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