title: Anti-anhedonic effect of deep brain stimulation of the prefrontal cortex and the dopaminergic reward system in a genetic rat model of depression: an intracranial self-stimulation paradigm study.
abstract: BACKGROUND
  One of the two core symptoms of major depression (MD), whether uni- or bipolar, is the inability to experience pleasure, suggested to be triggered by dysregulation within the brain reward system. In recent years, deep brain stimulation (DBS) has evolved as a potential tool to modulate pathological neural activity; stimulation of the subgenual cingulate (Cg25) has been shown to reduce depressive symptoms, including anhedonia. In rodents, the ventromedial prefrontal cortex (vmPFC) is likely to represent the correlate of Cg25 and accordingly, stimulation of vmPFC reduces anhedonia-like behavior in rats.
  
  
  OBJECTIVE
  The present study addresses the question of whether the anti-anhedonic effect of vmPFC-DBS is mediated by the brain reward system.
  
  
  METHODS
  Rats of the Flinders Sensitive Line (FSL), a validated genetic animal model of depression, and its controls, the Flinders Resistant Line (FRL), were stimulated in the vmPFC and tested in the forced swim test (FST), sucrose consumption test (SCT) and the intracranial self-stimulation (ICSS) paradigm. The curve-shift paradigm of ICSS was used in combination with vmPFC-DBS, d-amphetamine and fluoxetine to quantify reward-facilitating or -attenuating treatment effects.
  
  
  RESULTS
  Our findings support anti-depressive efficacy of vmPFC-DBS with respect to despair- and anhedonia-like behavior, as shown in the FST and SCT, respectively. However, DBS did not elicit reward-facilitating or reward-attenuating effects on ICSS behavior.
  
  
  CONCLUSIONS
  These data suggest that it is unlikely that the anti-anhedonic effect of vmPFC-DBS depends on the mesolimbic dopaminergic reward system.
authors.affiliation: International Graduate Program Medical Neurosciences, Charité University Hospital, Berlin, Germany.
authors.forename: Ellis
authors.initials: E
authors.lastname: Rea
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Gustav Carus Dresden, Technical University Dresden, Germany; International Graduate Program Medical Neurosciences, Charité University Hospital, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Rummel
authors.affiliation: Max Planck Institute for Human Development, Center for Adaptive Rationality (ARC), Berlin, Germany.
authors.forename: Timo T
authors.initials: TT
authors.lastname: Schmidt
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Gustav Carus Dresden, Technical University Dresden, Germany.
authors.forename: Ravit
authors.initials: R
authors.lastname: Hadar
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Gustav Carus Dresden, Technical University Dresden, Germany. Electronic address: christine.winter@uniklinikum-dresden.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation; D003865:Major Depressive Disorder / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000503:physiopathology*; D051381:Rats; D012201:Reward
chemical_list: D004298:Dopamine
keywords: Anhedonia; Deep brain stimulation; Flinders Sensitive Line; Intracranial self-stimulation; Major depression