Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats

Hamani, Clement; Diwan, Mustansir; Macedo, Carlos Eduardo; Brandão, Marcus Lira; Shumake, Jason; González-Lima, Francisco; Raymond, Roger; Lozano, Andrés M.; Fletcher, Paul; Nóbrega, José N.

doi:10.1016/j.biopsych.2009.08.025

Cited by 284 publications

(251 citation statements)

References 52 publications

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“…Yet, we decided not to pursue these experiments for various reasons. First, stimulation settings in our study were similar to those associated with antidepressant-like responses, serotonin release and increased BDNF expression in previous reports (Hamani et al, 2010b;Hamani and Temel, 2012). In our experience, currents above 300 μA are detrimental and may worsen behavioural responses in the forced swim test (Hamani et al, 2010a).…”

Section: Discussionsupporting

confidence: 79%

“…Similar to humans, DBS applied to homologous regions in rodents (i.e. the ventromedial prefrontal cortex, vmPFC, and Acb) has been shown to induce antidepressant-like responses in different behavioural tests (Gersner et al, 2010;Hamani et al, 2014Hamani et al, , 2010bHamani and Temel, 2012;Rea et al, 2014).…”

Section: Deep Brain Stimulation (Dbs) Is Currently Being Investigatedmentioning

confidence: 99%

“…In rodents, DBS increases levels of hippocampal serotonin (Adachi et al, 2005;Hamani et al, 2010b) and brain derived neurotrophic factor (Gersner et al, 2010;. In a recent series of studies, stimulation of limbic structures (Encinas et al, 2011;Hamani et al, 2011;Stone et al, 2011;Toda et al, 2008) or the Acb (Schmuckermair et al, 2013) has been shown to increase hippocampal neurogenesis.…”

Section: Deep Brain Stimulation (Dbs) Is Currently Being Investigatedmentioning

confidence: 99%

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Acute high frequency stimulation of the prefrontal cortex or nucleus accumbens does not increase hippocampal neurogenesis in rats

Winter

Bregman

Voget

et al. 2015

Journal of Psychiatric Research

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To date, the effects of deep brain stimulation (DBS) on hippocampal neurogenesis have been mainly characterized in the context of memory. Acute stimulation (i.e. for 1 h) of either the entorhinal cortex or the anterior thalamus increases both cell proliferation and survival. We investigate whether stimulation applied to targets being considered for the treatment of depression, namely the ventromedial prefrontal cortex (vmPFC) or nucleus accumbens (Acb), also increases hippocampal neurogenesis in rodents. Rats were treated with vmPFC or Acb DBS for 1 h at different settings. 5′-bromo-2′deoxyuridine (BrdU) was injected three days following stimulation onset and animals were sacrificed 24 h or 28 days later. Overall, we found that neither vmPFC nor Acb DBS increased hippocampal neurogenesis. In summary, the delivery of acute stimulation into targets homologous to those used in human depression trials does not increase hippocampal neurogenesis.

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Section: Discussionsupporting

confidence: 79%

Section: Deep Brain Stimulation (Dbs) Is Currently Being Investigatedmentioning

confidence: 99%

Section: Deep Brain Stimulation (Dbs) Is Currently Being Investigatedmentioning

confidence: 99%

See 1 more Smart Citation

Acute high frequency stimulation of the prefrontal cortex or nucleus accumbens does not increase hippocampal neurogenesis in rats

Winter

Bregman

Voget

et al. 2015

Journal of Psychiatric Research

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“…The nucleus accumbens shell was targeted given its known involvement in drug-consummatory behavior 8 using the following stereotactic coordinates relative to bregma (AP + 1.6, DV -8.5, ML ± 2.4). Stimulation parameters and duration were loosely based on previous published experience with DBS for the treatment of psychiatric disease 8,20,21 but can be adjusted depending on the experimenter's needs. Error bars are moderate and not all days reach significance indicating the range of responses that can be seen in behavioral assessments despite a clear treatment effect.…”

Section: Representative Resultsmentioning

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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“…Previous experiments from our lab have found that DBS applied to the rodent ventral medial prefrontal cortex (vmPFC) can also induce antidepressant-like effects (Hamani et al, 2010(Hamani et al, , 2012(Hamani et al, , 2014). This treatment model has provided a tool to directly probe how the nervous system is affected by stimulation and how physiological consequences are linked to depression.…”

Section: Introductionmentioning

confidence: 99%

Chronic deep brain stimulation of the rat ventral medial prefrontal cortex disrupts hippocampal–prefrontal coherence

Insel

Pilkiw

Nóbrega

et al. 2015

Experimental Neurology

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Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) has been used to treat patients with treatment-resistant depression. As in humans, DBS applied to the ventromedial prefrontal cortex of rats induces antidepressant-like responses. Physiological interactions between structures that play a role in depression and antidepressant treatment are still unknown. The present study examined the effect of DBS on inter-region communication by measuring the coherence of local field potentials in the rat infralimbic cortex (IL; homologue of the SCG) and one of its major afferents, the ventral hippocampus (VH). Rats received daily IL DBS treatment (100 μA, 90 μs, 130 Hz; 8 h/day). Recordings were conducted in unrestrained, behaving animals on the day before treatment, after 1 and 10 days of treatment, and 10 days stimulation offset. VH-IL coherence in the 2-4 Hz range was reduced in DBS-treated animals compared with shams after 10 days, but not after only 1 day of treatment. No effect of DBS was observed in the 6-10 Hz (theta) range, where coherence was generally high and could be further evoked with a loud auditory stimulus. Finally, coherence was not affected by fluoxetine (10 mg/kg), suggesting that the effects of DBS were not likely mediated by increased serotonin levels. While these data support the hypothesis that DBS disrupts communication between regions important for expectation-based control of emotion, they also suggest that lasting physiological effects require many days of treatment and, furthermore, may be specific to lower-frequency patterns, the nature and scope of which await further investigation.☆ NI, MP and CH designed the experiments; NI and MP performed the experiments; NI analyzed the data; NI, JN, WDH, KT, and CH wrote the paper.

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Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats

Cited by 284 publications

References 52 publications

Acute high frequency stimulation of the prefrontal cortex or nucleus accumbens does not increase hippocampal neurogenesis in rats

Acute high frequency stimulation of the prefrontal cortex or nucleus accumbens does not increase hippocampal neurogenesis in rats

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

Chronic deep brain stimulation of the rat ventral medial prefrontal cortex disrupts hippocampal–prefrontal coherence

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