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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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00243205_v77_n2_p130_Thanos |
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todo:paper_00243205_v77_n2_p130_Thanos2023-10-03T14:34:42Z Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking Thanos, P.K. Rivera, S.N. Weaver, K. Grandy, D.K. Rubinstein, M. Umegaki, H. Wang, G.J. Hitzemann, R. Volkow, N.D. Addiction Alcoholism Associative learning Gene therapy adenovirus vector alcohol complementary DNA DNA dopamine 2 receptor alcohol consumption alcohol metabolism animal experiment article controlled study DNA modification DNA transfer drinking behavior heterozygosity male mouse nonhuman nucleus accumbens receptor upregulation wild type 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00243205_v77_n2_p130_Thanos |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Addiction Alcoholism Associative learning Gene therapy adenovirus vector alcohol complementary DNA DNA dopamine 2 receptor alcohol consumption alcohol metabolism animal experiment article controlled study DNA modification DNA transfer drinking behavior heterozygosity male mouse nonhuman nucleus accumbens receptor upregulation wild type |
| spellingShingle |
Addiction Alcoholism Associative learning Gene therapy adenovirus vector alcohol complementary DNA DNA dopamine 2 receptor alcohol consumption alcohol metabolism animal experiment article controlled study DNA modification DNA transfer drinking behavior heterozygosity male mouse nonhuman nucleus accumbens receptor upregulation wild type Thanos, P.K. Rivera, S.N. Weaver, K. Grandy, D.K. Rubinstein, M. Umegaki, H. Wang, G.J. Hitzemann, R. Volkow, N.D. Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking |
| topic_facet |
Addiction Alcoholism Associative learning Gene therapy adenovirus vector alcohol complementary DNA DNA dopamine 2 receptor alcohol consumption alcohol metabolism animal experiment article controlled study DNA modification DNA transfer drinking behavior heterozygosity male mouse nonhuman nucleus accumbens receptor upregulation wild type |
| description |
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. |
| format |
JOUR |
| author |
Thanos, P.K. Rivera, S.N. Weaver, K. Grandy, D.K. Rubinstein, M. Umegaki, H. Wang, G.J. Hitzemann, R. Volkow, N.D. |
| author_facet |
Thanos, P.K. Rivera, S.N. Weaver, K. Grandy, D.K. Rubinstein, M. Umegaki, H. Wang, G.J. Hitzemann, R. Volkow, N.D. |
| author_sort |
Thanos, P.K. |
| title |
Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking |
| title_short |
Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking |
| title_full |
Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking |
| title_fullStr |
Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking |
| title_full_unstemmed |
Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: Effects on ethanol drinking |
| title_sort |
dopamine d2r dna transfer in dopamine d2 receptor-deficient mice: effects on ethanol drinking |
| url |
http://hdl.handle.net/20.500.12110/paper_00243205_v77_n2_p130_Thanos |
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