+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine

, : Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine. Plos One 5(6): E11038-E11038

Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R) availability in the brain. Such a decrease consequently alters the ratio of D1R:D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified. ETHICS STATEMENT: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT) and G protein coupled receptor associated sorting protein-1 (GASP-1) knock out (KO) mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine. Together, our data suggests that changes in the ratio of the D1:D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization.


PMID: 20543951

DOI: 10.1371/journal.pone.0011038

Other references

Cardas, A.; Nica, G., 1939: Duration of the period of artificial insemination in sheep. DURING October-November 1938, a total of 776 ewes were artificially inseminated at the Manzar Tighina farm belonging to the Faculty of Agriculture, Chisinau. As a rule 0.2 c.c. of a 1: 3 dilution of semen was introduced into the cervix uteri at th...

Brennan, S.O.; Borg, J.Y.; Shaw, G.J.; Caen, J.; George, P.M., 1991: Functional antithrombin-III variant (41 Pro----Leu) identified by liquid secondary ion mass spectrometry. A genetic variant of antithrombin with impaired heparin cofactor activity was identified in 4 members of a French family. Both the variant and normal antithrombin component were purified by affinity chromatography on heparin Sepharose. Reverse pha...

Shirai, T.; Konnai, S.; Ikebuchi, R.; Okagawa, T.; Suzuki, S.; Sunden, Y.; Onuma, M.; Murata, S.; Ohashi, K., 2012: Molecular cloning of bovine lymphocyte activation gene-3 and its expression characteristics in bovine leukemia virus-infected cattle. Lymphocyte activation gene-3 (LAG-3), a major histocompatibility complex (MHC) class II binding CD4 homologue has recently been shown as one of the mechanisms for down-regulating immune responses during chronic disease progression. For the first t...

Froehlich, Dean Kenneth, 1961: The effects of anxiety and types of stress upon verbal serial learning. Dissertation Absts 22(5): 1723-1724

Schultze, J.L.; Dorfman, D.M.; Michalak, S.; Gribben, J.G.; Nadler, L.M., 1997: Low level expression of B7-1 and B7-2 by germinal center lymphomas is sufficient to prevent tolerance but not to induce anti-tumor immunity. Blood 90(10 SUPPL 1 PART 1): 413A, Nov 15

Akieda-Asai, S.; Sugiyama, M.; Miyazawa, T.; Koda, S.; Okano, I.; Senba, K.; Poleni, P-Emile.; Hizukuri, Y.; Okamoto, A.; Yamahara, K.; Mutoh, E.; Aoyama, F.; Sawaguchi, A.; Furuya, M.; Miyazato, M.; Kangawa, K.; Date, Y., 2013: Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet. A high-fat diet (HFD) is a well-known contributing factor in the development of obesity. Most rats fed HFDs become obese. Those that avoid obesity when fed HFDs are considered diet resistant (DR). We performed a microarray screen to identify genes...

Kareiva P., 1986: Patchiness dispersal and species interactions consequences for communities of herbivorous insects. Diamond, J And T J Case (Ed ) Community Ecology Xxii+665p Harper And Row: New York, N Y , Usa; Cambridge, England Illus Maps 192-206

Haas, P-Jan.; van Strijp, J., 2007: Anaphylatoxins: their role in bacterial infection and inflammation. Activation of the complement system plays a crucial role in the pathogenesis of infection and inflammation. Especially the complement activation products C3a and C5a, known as the anaphylatoxins, are potent proinflammatory mediators. In addition...

Liu, Z.Q.; Muhkerjee, S.; Sahni, M.; McCormick-Davis, C.; Leung, K.; Li, Z.; Gattone, V.H.; Tian, C.; Doms, R.W.; Hoffman, T.L.; Raghavan, R.; Narayan, O.; Stephens, E.B., 1999: Derivation and biological characterization of a molecular clone of SHIV(KU-2) that causes AIDS, neurological disease, and renal disease in rhesus macaques. Previously, we described the derivation of a pathogenic strain of simian-human immunodeficiency virus (SHIV(KU-2)) consisting of the tat, rev, vpu, and env genes of HIV-1 (strain HXB2) in a genetic background of SIV(mac)239 that causes AIDS and pr...

Herbes S.E.; Beauchamp J.J., 1977: Toxic interaction of mixtures of 2 coal conversion effluent components resorcinol and 6 methyl quinoline to daphnia magna. Bulletin of Environmental Contamination & Toxicology 17(1): 25-32