Losing control

• Verfasst von: Pfarr, Simone [VerfasserIn]
• Verfasst von: Bartsch, Dusan [VerfasserIn]
• Verfasst von: Spanagel, Rainer [VerfasserIn]
• Verfasst von: Sommer, Wolfgang H. [VerfasserIn]
• Titel: Losing control
• Titelzusatz: excessive alcohol seeking after selective inactivation of cue-responsive neurons in the infralimbic cortex
• Verf.angabe: 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
• E-Jahr: 2015
• Jahr: July 29, 2015
• Umfang: 12 S.
• Fussnoten: Gesehen am 29.01.2018
• Titel Quelle: Enthalten in: The journal of neuroscience
• Ort Quelle: Washington, DC : Soc., 1981
• Jahr Quelle: 2015
• Band/Heft Quelle: 35(2015), 30, Seite 10750-10761
• ISSN Quelle: 1529-2401
• DOI: doi:10.1523/JNEUROSCI.0684-15.2015
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: alcohol self-administration
• Sach-SW: conditioned cues
• Sach-SW: Daun02 inactivation method
• Sach-SW: medial prefrontal cortex
• Sach-SW: neuronal ensembles
• Sach-SW: reinstatement
• K10plus-PPN: 1567824617

Abstract

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.