Increased dopamine receptor expression and anti-depressant response following deep brain stimulation of the medial forebrain bundle
| Autor: | Carson Hoffmann, Vijayasree V. Giridharan, Jair C. Soares, Christian Ruiz, Patrick Cotton, Travis Peery, Dustin Luse, Caroline Hussey, João Quevedo, Manoj P. Dandekar, Albert J. Fenoy |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Deep Brain Stimulation Dopamine Prefrontal Cortex Nucleus accumbens 03 medical and health sciences chemistry.chemical_compound Depressive Disorder Treatment-Resistant 0302 clinical medicine Internal medicine medicine Animals Rats Wistar Medial forebrain bundle Dopamine transporter Dopamine Plasma Membrane Transport Proteins biology Chemistry Receptors Dopamine D2 Dopaminergic Homovanillic acid Medial Forebrain Bundle Brain Antidepressive Agents Rats Psychiatry and Mental health Clinical Psychology 030104 developmental biology Endocrinology nervous system Dopamine receptor biology.protein Brain stimulation reward 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of affective disorders. 217 |
| ISSN: | 1573-2517 |
| Popis: | Among several potential neuroanatomical targets pursued for deep brain stimulation (DBS) for treating those with treatment-resistant depression (TRD), the superolateral-branch of the medial forebrain bundle (MFB) is emerging as a privileged location. We investigated the antidepressant-like phenotypic and chemical changes associated with reward-processing dopaminergic systems in rat brains after MFB-DBS.Male Wistar rats were divided into three groups: sham-operated, DBS-Off, and DBS-On. For DBS, a concentric bipolar electrode was stereotactically implanted into the right MFB. Exploratory activity and depression-like behavior were evaluated using the open-field and forced-swimming test (FST), respectively. MFB-DBS effects on the dopaminergic system were evaluated using immunoblotting for tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine receptors (D1-D5), and high-performance liquid chromatography for quantifying dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in brain homogenates of prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens (NAc).Animals receiving MFB-DBS showed a significant increase in swimming time without alterations in locomotor activity, relative to the DBS-Off (p0.039) and sham-operated groups (p0.014), indicating an antidepressant-like response. MFB-DBS led to a striking increase in protein levels of dopamine D2 receptors and DAT in the PFC and hippocampus, respectively. However, we did not observe appreciable differences in the expression of other dopamine receptors, TH, or in the concentrations of dopamine, DOPAC, and HVA in PFC, hippocampus, amygdala, and NAc.This study was not performed on an animal model of TRD.MFB-DBS rescues the depression-like phenotypes and selectively activates expression of dopamine receptors in brain regions distant from the target area of stimulation. |
| Databáze: | OpenAIRE |
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