An Evaluation of Neuroplasticity and Behavior After Deep Brain Stimulation of the Nucleus Accumbens in an Animal Model of Depression

Falowski, Steven; Sharan, Ashwini; Reyes, Beverly A.S.; Sikkema, Carl; Szot, Patricia; Bockstaele, Elisabeth J. Van

doi:10.1227/neu.0b013e3182237346

Cited by 77 publications

(44 citation statements)

References 49 publications

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“…Encounter stimulation increased c-Fos expression in the nucleus accumbens shell of group-and isolationreared mice to a similar degree. Activation of nucleus accumbens increases exploratory and social play behaviors in rats (Falowski et al, 2011;Trezza et al, 2011;van Kuyck et al, 2007). Thus, enhanced neuronal activity in the nucleus accumbens shell may contribute to social interactions in male group-and isolation-reared mice.…”

Section: Discussionmentioning

confidence: 99%

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

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Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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Isolation-reared male rodents show abnormal behaviors such as hyperlocomotion, aggressive behaviors, deficits of prepulse inhibition, and depression-and anxiety-like behaviors, but the neurochemical mechanism for the effects of psychological stress in these animals is not fully understood. This study examined the effects of social interactions between isolation-reared mice and intruder mice on brain monoaminergic systems. A cage was divided into two compartments by a mesh partition to prevent direct physical interactions. The 20-min encounter with an intruder elicited a restless and hyperexcitable state (hyperactivity) in male, but not in female, isolationreared mice, whereas encounters with a sleeping intruder or a novel object did not. Although the encounter did not affect prefrontal neuronal-activity-marker c-Fos expression, dopamine (DA) levels, or serotonin (5-HT) levels in male group-reared mice or female isolation-reared mice, it increased prefrontal c-Fos expression, DA levels, and 5-HT levels in male isolation-reared mice. Furthermore, encounter-induced increases in c-Fos expression in the dorsal raphe nucleus and ventral tegmental area, but not in the nucleus accumbens shell, were much greater in isolation-reared than group-reared male mice. A 5-HT 1A receptor agonist, a metabotropic glutamate 2/3 receptor agonist, and a gamma-aminobutyric acid A receptor agonist attenuated isolation-induced aggressive behaviors and encounter-induced hyperactivity, c-Fos expression in the prefrontal cortex and dorsal raphe nucleus, and increases in prefrontal 5-HT levels. These findings suggest that the prefrontal DA and 5-HT systems are activated by encounter stimulation in male isolationreared mice, and the encounter-induced activation of 5-HT system triggers the induction of some abnormal behaviors in male isolation-reared mice. Furthermore, this study implies that the encounter stimulation-induced signal has a pharmacological significance.

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Section: Discussionmentioning

confidence: 99%

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Ago

Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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“…A decrease in the number of DA neurons firing would functionally attenuate the influence of the DA system on this circuit. NAc core DBS has been reported to decrease the level of DA and its metabolites in medial pre-frontal cortex, which was associated with lower tyrosine hydroxylase expression (Sesia et al, 2010; Falowski et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Nucleus accumbens high-frequency stimulation selectively impacts nigrostriatal dopaminergic neurons

Sesia

Bizup

Grace

2013

Int. J. Neuropsychopharm.

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High-frequency stimulation of the nucleus accumbens, also known as deep brain stimulation (DBS), is currently used to alleviate obsessive compulsive symptoms when pharmacotherapy is ineffective. However, the mechanism by which DBS achieves its therapeutic actions is not understood. Imaging studies and the actions of dopaminergic drugs in untreated patients suggest that the dopamine (DA) system likely plays a role in the pathophysiology of obsessive compulsive disorder. Therefore, we examined whether DBS would impact the DA system as a potential component of its therapeutic actions. The activity of DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were recorded in anesthetized rats under high-frequency stimulation. DA neuron activity was measured in terms of number of neurons firing, average firing rate and firing pattern. DBS of the nucleus accumbens core did not significantly affect VTA activity or discharge pattern. On the other hand, DBS caused a potent decrease in the number of SNc DA neurons firing spontaneously. Such an effect could contribute to the disruption of pathological habit formation in the SNc-dorsal striatal projection system that may have therapeutic implications for the treatment of obsessive compulsive disorder.

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“…Ventral tegmental area stimulation in Flinders rats increased sucrose self-administration, improved social interaction, and increased exploratory behavior in a novelty suppressed feeding test (31). In the open field, both NAc and LHb stimulation increased exploratory behavior in naïve and Kyoto Wistar rats (28,30).…”

Section: Dbs Effects In Other Animal Modelsmentioning

confidence: 97%

“…In addition to the vmPFC, targets recently studied in animal models include the nucleus accumbens (NAc) (28,29), lateral habenula (LHb) (30), and ventral tegmental area (VTA) (31).…”

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confidence: 99%

Preclinical Studies Modeling Deep Brain Stimulation for Depression

Hamani¹,

Nóbrega²

2012

Biological Psychiatry

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Deep brain stimulation (DBS) is currently being investigated for the treatment of depression. Results of early clinical trials have been very promising, but the mechanisms responsible for the effects of DBS are still unknown. This article reviews behavioral findings of stimulation applied to different brain targets in rodents, with a particular focus on the ventromedial prefrontal cortex. Mechanisms and substrates involved in the antidepressant-like effects of DBS, including the role of local tissue inactivation, the modulation of fiber pathways in the vicinity of the electrodes, as well as the importance of the serotonergic system and brain derived neurotrophic factor are discussed. KeywordsAnimal models; deep brain stimulation; depression; fiber pathways; psychiatry; radiofrequency lesions; serotonin Deep brain stimulation (DBS) has been investigated for the treatment of depression with promising clinical results (1-11). Although preclinical research using electrical stimulation to study behavior has been conducted for over 50 years, results from animal studies did not comprise the rationale for the current use of DBS in depression. Experiments i n animal models to investigate substrates and mechanisms responsible for the antidepressant-like effects of DBS were only conducted after the initial clinical trials were published (2,7,8,(10)(11)(12).This article provides an overview of current findings and some of the emerging concepts from experiments with DBS in models of depression, with a particular focus on results obtained with ventromedial prefrontal cortex (vmPFC) stimulation in rodents. CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscript Choosing a Stimulation TargetThe medial surface of the frontal cortex in rodents has been subdivided into four cytoarchitectural regions: the agranular frontal cortex, anterior cingulate cortex (AC), prelimbic cortex (PL), and infralimbic cortex(IL)( Figure 1A)(13-15).Alternatively, it has also been subdivided into dorsal and ventral "systems," according to functional role as well as afferent and efferent projections (15). The dorsal system includes the frontal agranular cortex, AC, and dorsal PL and seems to be involved in the control of eye and head movements (14-16). The ventral system, comprises the IL and ventral aspects of the PL (vPL), projects mainly to the amygdala, hypothalamus, insula, and brainstem and has been suggested to play a role in autonomic control (17)(18)(19)(20). Vertes (21) proposed an alternative subdivision of the medial prefrontal cortex (PFC) in dorsal (frontal agranular cortex and AC) and ventral regions (PL and IL). To mimic the effects of subgenual cingulum (SCG) DBS in rodents, we have been applying stimulation to the vmPFC (12,(22)(23)(24)(25)(26), including IL and vPL.Overall, the limits of the vPL are hard to delineate. However, if an arbitrary line is traced dividing the PL into dorsal and ventral halves, the approximate anteroposterior, mediolateral, and dorsoventral dimensions of the vmPFC (including IL and vPL...

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An Evaluation of Neuroplasticity and Behavior After Deep Brain Stimulation of the Nucleus Accumbens in an Animal Model of Depression

Cited by 77 publications

References 49 publications

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Nucleus accumbens high-frequency stimulation selectively impacts nigrostriatal dopaminergic neurons

Preclinical Studies Modeling Deep Brain Stimulation for Depression

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