Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell. (February 2015)

• Record Type: Journal Article
• Authors: Pisanu, Augusta; Lecca, Daniele; Valentini, Valentina; Bahi, Amine; Dreyer, Jean-Luc; Cacciapaglia, Fabio; Scifo, Andrea; Piras, Giovanna; Cadoni, Cristina; Di Chiara, Gaetano
• Is Part Of: Neuropharmacology. Volume 89(2015)
• Page Start: 398
• Page End: 411
• Publication Date: 2015-02
• Subjects: D1a receptors -- Dopamine -- Nucleus accumbens shell -- Cocaine -- Self-administration -- RNA-interference; c-Fos-IR c-Fos immunoreactivity -- DA dopamine -- D1aR D1a receptor -- D1-IR D1a R immunoreactivity -- FR fixed ratio -- Lv-siRNA lentivirus expressing siRNA -- Lv-GFP lentivirus expressing green fluorescent protein -- NAc nucleus accumbens -- RNAi RNA interference -- SA self-administration -- siRNA short interfering RNA -- TH tyrosine hydroxylase -- TH-IR TH immunoreactivity; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2014.10.018
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: 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. Highlights: Differential role of dopamine in n. accumbens shell and core in cocaine reinforcement. Dopamine D1 receptors in the n. accumbens shell are essential for acquisition of cocaine but not heroin reinforcement. Cocaine reinforcement is dependent upon the dopamine D1 receptors of the n. accumbens shell. Heroin reinforcement is not dependent upon the dopamine D1 receptors of the n. accumbens shell.