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  Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens

Hadar, R., Vengeliene, V., Barroeta Hlusicke, E., Canals, S., Noori, H., Wieske, F., et al. (2016). Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens. Translational Psychiatry, 6(6), 1-9. doi:10.1038/tp.2016.100.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-79BE-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-C87F-1
Genre: Journal Article

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Hadar, R, Author
Vengeliene, V, Author
Barroeta Hlusicke, E, Author
Canals, S, Author              
Noori, HR1, Author              
Wieske, F, Author
Rummel, J, Author
Harnack, D, Author
Heinz, A, Author
Spanagel, R, Author
Winter, C, Author
Affiliations:
1Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany, ou_persistent22              

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 Abstract: Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse.

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 Dates: 2016-06
 Publication Status: Published in print
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 Identifiers: DOI: 10.1038/tp.2016.100
BibTex Citekey: HadarVBCNWRHHSW2016
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Title: Translational Psychiatry
Source Genre: Journal
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Pages: - Volume / Issue: 6 (6) Sequence Number: - Start / End Page: 1 - 9 Identifier: -