Losing control: excessive alcohol seeking after selective inactivation of cue-responsive neurons in the infralimbic cortex
Loss of control over drinking is a key deficit in alcoholism causally associated with malfunction of the medial prefrontal cortex (mPFC), but underlying molecular and cellular mechanisms remain unclear. Cue-induced reinstatement of alcohol seeking activates a subset of mPFC neurons in rats, identifi...
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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
July 29, 2015
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| In: |
The journal of neuroscience
Year: 2015, Jahrgang: 35, Heft: 30, Pages: 10750-10761 |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.0684-15.2015 |
| Online-Zugang: | Verlag, teilw. kostenfrei, Volltext: http://dx.doi.org/10.1523/JNEUROSCI.0684-15.2015 Verlag, teilw. kostenfrei, Volltext: http://www.jneurosci.org.ezproxy.medma.uni-heidelberg.de/content/35/30/10750 
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| Verfasserangaben: | Simone Pfarr, Marcus W. Meinhardt, Manuela L. Klee, Anita C. Hansson, Valentina Vengeliene, Kai Schönig, Dusan Bartsch, Bruce T. Hope, Rainer Spanagel, and Wolfgang H. Sommer |
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| 245 | 1 | 0 | |a Losing control |b excessive alcohol seeking after selective inactivation of cue-responsive neurons in the infralimbic cortex |c Simone Pfarr, Marcus W. Meinhardt, Manuela L. Klee, Anita C. Hansson, Valentina Vengeliene, Kai Schönig, Dusan Bartsch, Bruce T. Hope, Rainer Spanagel, and Wolfgang H. Sommer |
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| 520 | |a Loss of control over drinking is a key deficit in alcoholism causally associated with malfunction of the medial prefrontal cortex (mPFC), but underlying molecular and cellular mechanisms remain unclear. Cue-induced reinstatement of alcohol seeking activates a subset of mPFC neurons in rats, identified by their common expression of the activity marker cFos and comprised of both principal and interneurons. Here, we used cFos-lacZ and pCAG-lacZ transgenic rats for activity-dependent or nonselective inactivation of neurons, respectively, which by their lacZ encoded β-galactosidase activity convert the inactive prodrug Daun02 into the neurotoxin daunorubicin. We report that activity-dependent ablation of a neuronal ensemble in the infralimbic but not the prelimbic subregion induced excessive alcohol seeking. The targeted neuronal ensemble was specific for the cue-induced response because stress-induced reinstatement was not affected in these animals. Importantly, nonselective inactivation of infralimbic neurons, using pCAG-lacZ rats, was without functional consequence on the cue-induced reinstatement task. Thus, inhibitory control over alcohol seeking is exerted by distinct functional ensembles within the infralimbic cortex rather than by a general inhibitory tone of this region on the behavioral output. This indicates a high level of functional compartmentation within the rat mPFC whereat many functional ensembles could coexist and interact within the same subregion. | ||
| 650 | 4 | |a alcohol self-administration | |
| 650 | 4 | |a conditioned cues | |
| 650 | 4 | |a Daun02 inactivation method | |
| 650 | 4 | |a medial prefrontal cortex | |
| 650 | 4 | |a neuronal ensembles | |
| 650 | 4 | |a reinstatement | |
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| 700 | 1 | |a Spanagel, Rainer |d 1961- |e VerfasserIn |0 (DE-588)112706312 |0 (DE-627)521941261 |0 (DE-576)289740002 |4 aut | |
| 700 | 1 | |a Sommer, Wolfgang H. |e VerfasserIn |0 (DE-588)1025859626 |0 (DE-627)725315350 |0 (DE-576)370844076 |4 aut | |
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