Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking

Panayotis K. Thanos, Seth N. Rivera, Katrina Weaver, David Grandy, Marcelo Rubinstein, Hiroyuki Umegaki, Gene Jack Wang, Robert Hitzemann, Nora D. Volkow

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)130-139
Number of pages10
JournalLife Sciences
Volume77
Issue number2
DOIs
StatePublished - May 27 2005

Fingerprint

Dopamine D2 Receptors
Drinking
Ethanol
Alcohols
Alcohol Drinking
DNA
Nucleus Accumbens
Up-Regulation
Drinking Behavior
Bottles
mouse DRD2 protein
Metabolism
Rats
Dopamine
Complementary DNA

Keywords

  • Addiction
  • Alcoholism
  • Associative learning
  • Gene therapy

ASJC Scopus subject areas

  • Pharmacology

Cite this

Thanos, P. K., Rivera, S. N., Weaver, K., Grandy, D., Rubinstein, M., Umegaki, H., ... Volkow, N. D. (2005). Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking. Life Sciences, 77(2), 130-139. https://doi.org/10.1016/j.lfs.2004.10.061

Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice : Effects on ethanol drinking. / Thanos, Panayotis K.; Rivera, Seth N.; Weaver, Katrina; Grandy, David; Rubinstein, Marcelo; Umegaki, Hiroyuki; Wang, Gene Jack; Hitzemann, Robert; Volkow, Nora D.

In: Life Sciences, Vol. 77, No. 2, 27.05.2005, p. 130-139.

Research output: Contribution to journalArticle

Thanos, PK, Rivera, SN, Weaver, K, Grandy, D, Rubinstein, M, Umegaki, H, Wang, GJ, Hitzemann, R & Volkow, ND 2005, 'Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking', Life Sciences, vol. 77, no. 2, pp. 130-139. https://doi.org/10.1016/j.lfs.2004.10.061
Thanos PK, Rivera SN, Weaver K, Grandy D, Rubinstein M, Umegaki H et al. Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking. Life Sciences. 2005 May 27;77(2):130-139. https://doi.org/10.1016/j.lfs.2004.10.061
Thanos, Panayotis K. ; Rivera, Seth N. ; Weaver, Katrina ; Grandy, David ; Rubinstein, Marcelo ; Umegaki, Hiroyuki ; Wang, Gene Jack ; Hitzemann, Robert ; Volkow, Nora D. / Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice : Effects on ethanol drinking. In: Life Sciences. 2005 ; Vol. 77, No. 2. pp. 130-139.
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