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    
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.
Paola Devoto; Giovanna Flore; Pierluigi Saba; Valentina Bini; Gian Luigi Gessa
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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.
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.
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