Document Detail


The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.
MedLine Citation:
PMID:  23289939     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α(2) -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α(2) -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex.
Authors:
Paola Devoto; Giovanna Flore; Pierluigi Saba; Valentina Bini; Gian Luigi Gessa
Related Documents :
15138119 - Gamma-hydroxybutyrate protects the liver from warm ischemia-reperfusion injury in rat.
9683439 - Mechanisms of cardioprotection by peroxynitrite in myocardial ischemia and reperfusion ...
15612529 - Ischemia and reperfusion of liver induces enos and inos expression: effects of a no don...
8370109 - 1,4:3,6-dianhydrohexitol nitrate derivatives. i. synthesis and antianginal activity of ...
16398819 - Protective effect of erythropoietin on renal ischemia and reperfusion injury.
18287879 - Possible involvement of erythropoietin in remote renal preconditioning-induced cardiopr...
18332859 - Endothelium removal augments endothelium-independent vasodilatation in rat mesenteric v...
1464279 - N-methyl-d-aspartate injection into the massa intermedia facilitates development of lim...
6812149 - Radial maze as a tool for assessing the effect of drugs on the working memory of rats.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-7
Journal Detail:
Title:  Addiction biology     Volume:  -     ISSN:  1369-1600     ISO Abbreviation:  Addict Biol     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9604935     Medline TA:  Addict Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.
Affiliation:
Department of Biomedical Sciences, Neuroscience and Clinical Pharmacology Division, University of Cagliari, Italy; Center of Excellence 'Neurobiology of Addiction', University of Cagliari, Italy; 'Guy Everett Laboratory', University of Cagliari, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Genomic Signatures of a Global Fitness Index in a Multi-Ethnic Cohort of Women.
Next Document:  Characterization of set Intermediate Restorative Material, Biodentine, Bioaggregate and a prototype ...