Behavioral sensitization and cellular responses to psychostimulants are reduced in D2R knockout mice

Autor: Ramon Trullas, Patricia García-Sanz, Noelia Granado, Rafael Maldonado, M. Gustavo Murer, Ana B. Martín, Oscar Solís, Rosario Moratalla, Petar Podlesniy, Adrián Sanz-Magro
Přispěvatelé: Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Fundación Ramón Areces, Agencia Nacional de Promoción Científica y Tecnológica (Argentina), Universidad de Buenos Aires, Generalitat de Catalunya, Agència de Gestió d'Ajuts Universitaris i de Recerca
Rok vydání: 2019
Předmět:
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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ISSN: 1369-1600
1355-6215
Popis: Repeated cocaine exposure causes long-lasting neuroadaptations that involve alterations in cellular signaling and gene expression mediated by dopamine in different brain regions, such as the striatum. Previous studies have pointed out to the dopamine D1 receptor as one major player in psychostimulants-induced behavioral, cellular, and molecular changes. However, the role of other dopamine receptors has not been fully characterized. Here we used dopamine D2 receptor knockout (D2−/−) mice to explore the role of D2 receptor (D2R) in behavioral sensitization and its associated gene expression after acute and chronic cocaine and amphetamine administration. We also studied the impact of D2R elimination in D1R-mediated responses. We found that cocaine- and amphetamine-induced behavioral sensitization is deficient in D2−/− mice. The expression of dynorphin, primarily regulated by D1R and a marker of direct-pathway striatal neurons, is attenuated in naïve- and in cocaine- or amphetamine-treated D2−/− mice. Moreover, c-Fos expression observed in D2−/− mice was reduced in acutely but not in chronically treated animals. Interestingly, inactivation of D2R increased c-Fos expression in neurons of the striatopallidal pathway. Finally, elimination of D2R blunted the locomotor and striatal c-Fos response to the full D1 agonist SKF81297. In conclusion, D2R is critical for the development of behavioral sensitization and the associated gene expression, after cocaine administration, and it is required for the locomotor responses promoted by D1R activation.
This work was supported by grants from the Spanish Ministries of Innovation, Science and Universities (SAF2016-78207-R and PCIN2015-098 to R. Moratalla, SAF2017-84060-R-AEI/FEDER-UE to R. Maldonado, and SAF2017-89791-R to P. Podlesniy and R. Trullas) and Health, Social Services and Equality (PNSD 2016/033 and CIBERNED CB06/05/0055 to R. Moratalla and RETICS/RTA, RD16/0017 to R.Maldonado.) and from the Ramón Areces Foundation (172275 and OTR02679) to R. Moratalla and ANPCYT (Agency for the Promotion of Science and Technology, Argentina), PICT 2013 1523 and 2015 3687 and by the University of Buenos Aires (UBACYT 2018) to M.G.M. and the Catalan Government (AGAUR, #ICREA Acadèmia-2015 and #2017-SGR-669) to R. Maldonado.
Databáze: OpenAIRE
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