title: Chronic deep brain stimulation of the medial forebrain bundle reverses depressive-like behavior in a hemiparkinsonian rodent model.
abstract: Preclinical and clinical evidence suggests that depression might be associated with a dysfunction in the reward/motivation circuitry. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has been shown in a recent clinical trial to provide a prompt and consistent improvement of depressive symptoms in treatment-resistant patients. In order to better understand the underlying mechanisms of neuromodulation in the context of depression, the effects of chronic bilateral MFB-DBS were assessed in a combined rodent model of depression and Parkinson's disease. Female Sprague-Dawley rats received unilateral 6-OHDA injection in the right MFB and were divided into three groups: CMS-STIM, CMS-noSTIM and control group. The CMS groups were submitted to chronic unpredictable mild stress (CMS) protocol for 6 weeks. MFB-DBS was applied only to the CMS-STIM group for 1 week. All groups were repeatedly probed on a series of behavioral tasks following each intervention, and to a postmortem histological analysis. CMS led to an increase in immobility in the forced swim test, to a decrease in sucrose solution consumption in the sucrose preference test, as well as to an increased production of ultrasonic vocalizations in the 22 kHz range, indicating increased negative affect. MFB-DBS reversed the anhedonic-like and despair-like behaviors. The results suggest that unilateral dopamine depletion did not preclude MFB-DBS in reversing depressive-like and anhedonic-like behavior in the rodent. Further understanding of the importance of hemispheric dominance in neuropsychiatric disorders is essential in order to optimize stimulation as a therapeutic strategy in these diseases.
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Freiburg-Medical Center, Breisacher Str. 64, 79106, Freiburg, Germany. luciano.furlanetti@uniklinik-freiburg.de.
authors.forename: Luciano L
authors.initials: LL
authors.lastname: Furlanetti
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Freiburg-Medical Center, Breisacher Str. 64, 79106, Freiburg, Germany.
authors.forename: Volker A
authors.initials: VA
authors.lastname: Coenen
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Freiburg-Medical Center, Breisacher Str. 64, 79106, Freiburg, Germany.
authors.forename: Iñigo A
authors.initials: IA
authors.lastname: Aranda
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Freiburg-Medical Center, Breisacher Str. 64, 79106, Freiburg, Germany.
authors.forename: Máté D
authors.initials: MD
authors.lastname: Döbrössy
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D046690:Deep Brain Stimulation / Q000379:methods*; D003866:Depressive Disorder / Q000209:etiology* / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D008474:Medial Forebrain Bundle / Q000293:injuries / Q000378:metabolism / Q000502:physiology*; D009068:Movement / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000150:complications* / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000209:etiology / Q000628:therapy; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014828:Vocalization, Animal / Q000187:drug effects / Q000502:physiology
chemical_list: D018663:Adrenergic Agents; D000697:Central Nervous System Stimulants; D016627:Oxidopamine; D000661:Amphetamine
keywords: Chronic mild stress; Deep brain stimulation; Depression; Medial forebrain bundle; Rat model