Journal article

Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell

  • Pisanu, Augusta Institute of Neuroscience, National Research Council of Italy, Cagliari, Italy
  • Lecca, Daniele Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Italy - National Institute of Neuroscience, University of Cagliari, Italy
  • Valentini, Valentina Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Italy - National Institute of Neuroscience, University of Cagliari, Italy - Centre of Excellence ‘Neurobiology of Dependence’, University of Cagliari, Italy
  • Bahi, Amine Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
  • Dreyer, Jean-Luc Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
  • Cacciapaglia, Fabio Department of Toxicology, University of Cagliari, Italy
  • Scifo, Andrea Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Italy
  • Piras, Giovanna Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Italy - National Institute of Neuroscience, University of Cagliari, Italy
  • Cadoni, Cristina Institute of Neuroscience, National Research Council of Italy, Cagliari, Italy - National Institute of Neuroscience, University of Cagliari, Italy - Centre of Excellence ‘Neurobiology of Dependence’, University of Cagliari, Italy
  • Chiara, Gaetano Di Institute of Neuroscience, National Research Council of Italy, Cagliari, Italy - Department of Biomedical Sciences, Neuropsychopharmacology Section, University of Cagliari, Italy - National Institute of Neuroscience, University of Cagliari, Italy - Centre of Excellence ‘Neurobiology of Dependence’, University of Cagliari, Italy
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    01.02.2015
Published in:
  • Neuropharmacology. - 2015, vol. 89, p. 398–411
English Microdialysis during i.v. drug self-administration (SA) have implicated nucleus accumbens (NAc) shell DA in cocaine and heroin reinforcement. However, this correlative evidence has not been yet substantiated by experimental evidence obtained by studying the effect of selective manipulation of NAc shell DA transmission on cocaine and heroin SA. In order to investigate this issue, DA D1a receptor (D1aR) expression was impaired in the NAc shell and core by locally infusing lentiviral vectors (LV) expressing specific D1aR-siRNAs (LV-siRNAs). Control rats were infused in the same areas with LV expressing GFP. Fifteen days later, rats were trained to acquire i.v. cocaine or heroin self-administration (SA). At the end of behavioral experiments, in order to evaluate the effect of LV-siRNA on D1aR expression, rats were challenged with amphetamine and the brains were processed for immunohistochemical detection of c-Fos and D1aR. Control rats acquired i.v. cocaine and heroin SA. Infusion of LV-siRNAs in the medial NAc shell reduced D1aR density and the number of c-Fos positive nuclei in the NAc shell, while sparing the core, and prevented the acquisition of cocaine, but not heroin SA. In turn, LV-siRNAs infusion in the core reduced D1aR density and the number of c-Fos positive nuclei in the same area, while sparing the shell, and failed to affect acquisition of cocaine. The differential effect of LV impairment of NAc shell D1aR on cocaine and heroin SA indicates that NAc shell DA acting on D1aR specifically mediates cocaine reinforcement.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/304155
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