title: The antidepressant effects of ventromedial prefrontal cortex stimulation is associated with neural activation in the medial part of the subthalamic nucleus.
abstract: The nucleus accumbens (NAc), ventromedial prefrontal cortex (vmPFC), and cingulate gyrus (Cg) are key regions in the control of mood-related behaviors. Electrical stimulation of these areas induces antidepressant-like effects in both patients and animal models. Another structure whose limbic connections are receiving more interest in the context of mood-related behaviors is the medial part of the subthalamic nucleus (STN). Here, we tested the hypothesis that the mood-related effects of NAc, vmPFC, and Cg are accompanied by changes in the neural activity of the STN. We performed high-frequency stimulation (HFS) of the NAc, vmPFC, and Cg. Animals were behaviorally tested for hedonia and forced swim immobility; and the cellular activities in the different parts of the STN were assessed by means of c-Fos immunoreactivity (c-Fos-ir). Our results showed that HFS of the NAc and vmPFC, but not Cg reduced anhedonic-like and forced swim immobility behaviors. Interestingly, there was a significant increase of c-Fos-ir in the medial STN with HFS of the vmPFC, but not the NAc and Cg as compared to the sham. Correlation analysis showed that the medial STN is associated with the antidepressant-like behaviors in vmPFC HFS animals. No behavioral correlation was found with respect to behavioral outcome and activity in the lateral STN. In conclusion, HFS of the vmPFC induced profound antidepressant-like effects with enhanced neural activity in the medial part of the STN.
authors.affiliation: Department of Biological Sciences, Sunway University, Bandar Sunway, Malaysia. Electronic address: drlimleewei@gmail.com.
authors.forename: Lee Wei
authors.initials: LW
authors.lastname: Lim
authors.affiliation: Department of Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Neurology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Marcus L F
authors.initials: ML
authors.lastname: Janssen
authors.affiliation: Department of Neurosurgery, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Ersoy
authors.initials: E
authors.lastname: Kocabicak
authors.affiliation: Department of Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Neurosurgery, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: y.temel@maastrichtuniversity.nl.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Temel
mesh_terms: D000818:Animals; D003863:Depression / Q000503:physiopathology*; D004558:Electric Stimulation; D006179:Gyrus Cinguli / Q000378:metabolism; D008297:Male; D009043:Motor Activity; D009714:Nucleus Accumbens / Q000378:metabolism; D017397:Prefrontal Cortex / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological; D020531:Subthalamic Nucleus / Q000378:metabolism / Q000503:physiopathology*; D013550:Swimming
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: Cingulate gyrus (Cg); High-frequency stimulation (HFS); Nucleus accumbens (NAc); Subthalamic nucleus (STN); Ventromedial prefrontal cortex (vmPFC)