Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens.
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.
Department of Psychiatry and Psychotherapy, University Hospital Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
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Hadar
Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Vengeliene
Department of Psychiatry and Psychotherapy, University Hospital Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
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Barroeta Hlusicke
Cellular and Systems Neurobiology Unit, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Sant Joan d'Alacant, Spain.
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Canals
Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Noori
Department of Psychiatry and Psychotherapy, University Hospital Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
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Wieske
Department of Psychiatry and Psychotherapy, University Hospital Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
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J
Rummel
Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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Harnack
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
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A
Heinz
Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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R
Spanagel
Department of Psychiatry and Psychotherapy, University Hospital Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
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C
Winter
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D002421:Caudate Nucleus / Q000503:physiopathology; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009714:Nucleus Accumbens / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology; D011699:Putamen / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence
D004298:Dopamine