Programmed deep brain stimulation synchronizes VTA gamma band field potential and alleviates depressive-like behavior in rats

Gazit, Tomer; Friedman, Alexander; Lax, Elad; Samuel, Merav; Zahut, Roy; Katz, Miriam; Abraham, Lital; Tischler, Hadass; Teicher, Mina; Yadid, Gal

doi:10.1016/j.neuropharm.2014.12.003

Cited by 35 publications

(30 citation statements)

References 40 publications

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“…The VTA, a central structure of the reward network, has been of interest in clinical research for MDD (Gazit et al, 2015; Furlanetti et al, 2016). This region contains the dopaminergic neurons of the mesocortical and mesolimbic circuitry, which project via the medial forebrain bundle (MFB) to the medial prefrontal cortex (mPFC), the NAc, the hippocampus, and the amygdala (Russo and Nestler, 2013).…”

Section: Introductionmentioning

confidence: 99%

Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation

et al. 2017

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Background: The ventral tegmental area (VTA), containing mesolimbic and mesocortical dopaminergic neurons, is implicated in processes involving reward, addiction, reinforcement, and learning, which are associated with a variety of neuropsychiatric disorders. Electrical stimulation of the VTA or the medial forebrain bundle and its projection target the nucleus accumbens (NAc) is reported to improve depressive symptoms in patients affected by severe, treatment-resistant major depressive disorder (MDD) and depressive-like symptoms in animal models of depression. Here we sought to determine the neuromodulatory effects of VTA deep brain stimulation (DBS) in a normal large animal model (swine) by combining neurochemical measurements with functional magnetic resonance imaging (fMRI).Methods: Animals (n = 8 swine) were implanted with a unilateral DBS electrode targeting the VTA. During stimulation (130 Hz frequency, 0.25 ms pulse width, and 3 V amplitude), fMRI was performed. Following fMRI, fast-scan cyclic voltammetry in combination with carbon fiber microelectrodes was performed to quantify VTA-DBS-evoked dopamine release in the ipsilateral NAc. In a subset of swine, the blood oxygen level-dependent (BOLD) percent change evoked by stimulation was performed at increasing voltages (1, 2, and 3 V).Results: A significant increase in VTA-DBS-evoked BOLD signal was found in the following regions: the ipsilateral dorsolateral prefrontal cortex, anterior and posterior cingulate, insula, premotor cortex, primary somatosensory cortex, and striatum. A decrease in the BOLD signal was also observed in the contralateral parahippocampal cortex, dorsolateral and anterior prefrontal cortex, insula, inferior temporal gyrus, and primary somatosensory cortex (Bonferroni-corrected < 0.001). During neurochemical measurements, stimulation time-locked changes in dopamine release were recorded in the NAc, confirming that mesolimbic dopaminergic neurons were stimulated by DBS. In the parametric study, BOLD signal changes were positively correlated with stimulation amplitude.Conclusions: In this study, the modulation of the neural circuitry associated with VTA-DBS was characterized in a large animal. Our findings suggest that VTA-DBS could affect the activity of neural systems and brain regions implicated in reward, mood regulation, and in the pathophysiology of MDD. In addition, we showed that a combination of fMRI and electrochemically-based neurochemical detection platform is an effective investigative tool for elucidating the circuitry involved in VTA-DBS.

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Section: Introductionmentioning

confidence: 99%

Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation

et al. 2017

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“…Although the exact mechanisms of deep brain stimulation are not fully characterized, DBS efficacy for both motor and psychiatric disorders may result from a dynamic interaction between the electrical therapy and the functioning of various subcortical and cortical brain regions over time 6,[22][23][24][25][26] . While non-contingent methods of methamphetamine delivery to rodents are well-described 27,28 , these methods are most appropriate for discrete investigations of drug pharmacokinetics and neurochemical effects [27][28][29] .…”

Section: Discussionmentioning

confidence: 99%

“…The methods we have described will allow investigators to develop and refine treatment strategies that can modify drug-related behavior while being delivered outside of the drug environment in a restricted timeframe. There is accumulating evidence that transient intracranial electrical stimulation that is patterned after specific neurophysiological deficits 23 or combined with systemic pharmacotherapy 36 exert long-lasting positive effects on psychiatric and drug-related behaviors for several weeks after the treatment has ceased.…”

Section: Discussionmentioning

confidence: 99%

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Batra

Guerin

Goeders

et al. 2016

JoVE

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Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

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“…Studies applying DBS in rats report antidepressant effects for DBS to the ventromedial prefrontal cortex (vmPFC, rodent analogue of Cg25, Hamani et al, 2010a,b;Rea et al, 2014), Nacc (Gersner et al, 2010), MFB (Edemann-Callesen et al, 2015), ventral tegmental area (VTA, Gazit et al, 2015) and lateral habenula (LHb, Meng et al, 2011). Most of these investigations however have been carried out in naïve rats or in single animal models of depression.…”

Section: Introductionmentioning

confidence: 99%

“…Using the validated FSL rat model of depressionOverstreet, 1993;Overstreet et al, 2005, Overstreet andWegener, 2013) we addressed these concerns and could underline the potential of DBS as an anti-depressive therapy. Still, FSL rats constitute a model of therapy-responsive depression, for which all groups of clinically applied antidepressant therapies ranging from SSRIs and tricyclics over electroconvulsive therapy to DBS have been demonstrated effective(Edemann-Callesen et al, 2015;Gazit et al, 2015; …”

mentioning

confidence: 99%

Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression

Rummel¹,

Voget

Hadar

et al. 2016

Journal of Psychiatric Research

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Programmed deep brain stimulation synchronizes VTA gamma band field potential and alleviates depressive-like behavior in rats

Cited by 35 publications

References 40 publications

Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation

Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression

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