Journal Home > Volume 10 , Issue 1
Objective:

Deep brain stimulation (DBS) has promising outcomes in treatment-resistant depression (TRD). Several regions, including the subcallosal cingulate gyrus (SCG), nucleus accumbens, ventral capsule/ ventral striatum, and lateral habenula (LHb), can be targeted for TRD treatment. However, which target provides the best results remains controversial.

Methods:

We evaluated the antidepressant and antianxiety effects of DBS of the ventral medial prefrontal cortex (vmPFC) and LHb in stressed rats using the forced swimming test (FST) and open field test (OFT).

Results:

Bilateral high-frequency DBS of the vmPFC and LHb induced a significant decrease of the immobility time compared with that of controls (p < 0.05) in the FST. In the OFT, rats receiving vmPFC and LHb DBS showed no difference in the number of entries and time spent in the center area compared with those of control rats. However, vmPFC DBS provoked a significant decrease of these parameters compared with those of rats receiving LHb DBS (p < 0.05).

Conclusion:

These results suggested that vmPFC and LHb DBS had similar antidepressant effects, whereas LHb DBS was more effective in reducing anxiety-like behaviors. The results provide a reference for high-frequency DSB of SCG and LHb in TRD.


menu
Abstract
Full text
Outline
About this article

Effects of lateral habenula and ventral medial prefrontal cortex deep brain stimulation in rats

Show Author's information Tengteng Fan1,§Yuqi Zhang2,§Zhiyan Wang3( )Ming Yi2Naizheng Liu2Chunhua Hu3Lei Luo1( )
Peking University The Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100871, China
National Engineering Laboratory for Neuromodulation, Tsinghua University School of Aerospace Engineering, Tsinghua University, Beijing 100084, China

§ These authors contributed equally to this work.

Abstract

Objective:

Deep brain stimulation (DBS) has promising outcomes in treatment-resistant depression (TRD). Several regions, including the subcallosal cingulate gyrus (SCG), nucleus accumbens, ventral capsule/ ventral striatum, and lateral habenula (LHb), can be targeted for TRD treatment. However, which target provides the best results remains controversial.

Methods:

We evaluated the antidepressant and antianxiety effects of DBS of the ventral medial prefrontal cortex (vmPFC) and LHb in stressed rats using the forced swimming test (FST) and open field test (OFT).

Results:

Bilateral high-frequency DBS of the vmPFC and LHb induced a significant decrease of the immobility time compared with that of controls (p < 0.05) in the FST. In the OFT, rats receiving vmPFC and LHb DBS showed no difference in the number of entries and time spent in the center area compared with those of control rats. However, vmPFC DBS provoked a significant decrease of these parameters compared with those of rats receiving LHb DBS (p < 0.05).

Conclusion:

These results suggested that vmPFC and LHb DBS had similar antidepressant effects, whereas LHb DBS was more effective in reducing anxiety-like behaviors. The results provide a reference for high-frequency DSB of SCG and LHb in TRD.

Keywords:

lateral habenula, ventral medial prefrontal cortex, deep brain stimulation, depression
Received: 10 January 2022 Revised: 22 February 2022 Accepted: 23 February 2022 Published: 01 April 2022 Issue date: March 2022
References(34)
[1]
Dandekar MP, Fenoy AJ, Carvalho AF, et al. Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications. Mol Psychiatry 2018, 23(5): 1094-1112.
[2]
Hitti FL, Yang AI, Cristancho MA, et al. Deep brain stimulation is effective for treatment-resistant depression: a meta-analysis and meta-regression. J Clin Med 2020, 9(9): E2796.
[3]
Mayberg HS, Lozano AM, Voon V, et al. Deep brain stimulation for treatment-resistant depression. Neuron 2005, 45(5): 651-660.
[4]
Sartorius A, Kiening KL, Kirsch P, et al. Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry 2010, 67(2): e9-e11.
[5]
Holtzheimer PE, Kelley ME, Gross RE, et al. Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Arch Gen Psychiatry 2012, 69(2): 150-158.
[6]
Holtzheimer PE, Husain MM, Lisanby SH, et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry 2017, 4(11): 839-849.
[7]
Zhang CC, Kim SG, Li DY, et al. Habenula deep brain stimulation for refractory bipolar disorder. Brain Stimul 2019, 12(5): 1298-1300.
[8]
Wang ZY, Cai XD, Qiu RR, et al. Case report: lateral habenula deep brain stimulation for treatment-resistant depression. Front Psychiatry 2021, 11: 616501.
[9]
Torres-Sanchez S, Perez-Caballero L, Berrocoso E. Cellular and molecular mechanisms triggered by Deep Brain Stimulation in depression: a preclinical and clinical approach. Prog Neuropsychopharmacol Biol Psychiatry 2017, 73: 1-10.
[10]
Harro J. Animal models of depression: pros and cons. Cell Tissue Res 2019, 377(1): 5-20.
[11]
Matsumoto M, Hikosaka O. Lateral habenula as a source of negative reward signals in dopamine neurons. Nature 2007, 447(7148): 1111-1115.
[12]
He NY, Sethi SK, Zhang CC, et al. Visualizing the lateral habenula using susceptibility weighted imaging and quantitative susceptibility mapping. Magn Reson Imaging 2020, 65: 55-61.
[13]
Hamani C, Diwan M, Macedo CE, et al. Antidepressant- like effects of medial prefrontal cortex deep brain stimulation in rats. Biol Psychiatry 2010, 67(2): 117-124.
[14]
Hamani C, Machado DC, Hipólide DC, et al. Deep brain stimulation reverses anhedonic-like behavior in a chronic model of depression: role of serotonin and brain derived neurotrophic factor. Biol Psychiatry 2012, 71(1): 30-35.
[15]
Hamani C, Amorim BO, Wheeler AL, et al. Deep brain stimulation in rats: different targets induce similar antidepressant-like effects but influence different circuits. Neurobiol Dis 2014, 71: 205-214.
[16]
Tchenio A, Lecca S, Valentinova K, et al. Limiting habenular hyperactivity ameliorates maternal separation- driven depressive-like symptoms. Nat Commun 2017, 8(1): 1135.
[17]
Weersing VR, Gonzalez A, Campo JV, et al. Brief behavioral therapy for pediatric anxiety and depression: piloting an integrated treatment approach. Cogn Behav Pract 2008, 15(2): 126-139.
[18]
Sørensen MJ, Nissen JB, Mors O, et al. Age and gender differences in depressive symptomatology and comorbidity: an incident sample of psychiatrically admitted children. J Affect Disord 2005, 84(1): 85-91.
[19]
Yang Y, Cui YH, Sang KN, et al. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature 2018, 554(7692): 317-322.
[20]
Hamani C, Diwan M, Isabella S, et al. Effects of different stimulation parameters on the antidepressant- like response of medial prefrontal cortex deep brain stimulation in rats. J Psychiatr Res 2010, 44(11): 683-687.
[21]
Li B, Piriz J, Mirrione M, et al. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature 2011, 470(7335): 535-539.
[22]
Mayberg HS. Targeted electrode-based modulation of neural circuits for depression. J Clin Invest 2009, 119(4): 717-725.
[23]
McInerney SJ, McNeely HE, Geraci J, et al. Neurocognitive predictors of response in treatment resistant depression to subcallosal cingulate gyrus deep brain stimulation. Front Hum Neurosci 2017, 11: 74.
[24]
Merkl A, Aust S, Schneider GH, et al. Deep brain stimulation of the subcallosal cingulate gyrus in patients with treatment-resistant depression: a double-blinded randomized controlled study and long-term follow-up in eight patients. J Affect Disord 2018, 227: 521-529.
[25]
Zhang CC, Zhang YY, Luo HC, et al. Bilateral Habenula deep brain stimulation for treatment-resistant depression: clinical findings and electrophysiological features. Transl Psychiatry 2022, 12(1): 52.
[26]
Lim LW, Prickaerts J, Huguet G, et al. Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms. Transl Psychiatry 2015, 5: e535.
[27]
Jiménez-Sánchez L, Castañé A, Pérez-Caballero L, et al. Activation of AMPA receptors mediates the antidepressant action of deep brain stimulation of the infralimbic prefrontal cortex. Cereb Cortex 2016, 26(6): 2778-2789.
[28]
Kim Y, Morath B, Hu CL, et al. Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex. Behav Brain Res 2016, 306: 170-177.
[29]
Kale´n P, Strecker RE, Rosengren E, et al. Regulation of striatal serotonin release by the lateral habenula- dorsal raphe pathway in the rat as demonstrated by in vivo microdialysis: role of excitatory amino acids and GABA. Brain Res 1989, 492(1/2): 187-202.
[30]
Meng HM, Wang YN, Huang M, et al. Chronic deep brain stimulation of the lateral habenula nucleus in a rat model of depression. Brain Res 2011, 1422: 32-38.
[31]
Torres-Sanchez S, Perez-Caballero L, Mico JA, et al. Effect of deep brain stimulation of the ventromedial prefrontal cortex on the noradrenergic system in rats. Brain Stimul 2018, 11(1): 222-230.
[32]
Veerakumar A, Challis C, Gupta P, et al. Antidepressant-like effects of cortical deep brain stimulation coincide with pro-neuroplastic adaptations of serotonin systems. Biol Psychiatry 2014, 76(3): 203-212.
[33]
Garber J, Brunwasser SM, Zerr AA, et al. Treatment and prevention of depression and anxiety in youth: test of cross-over effects. Depress Anxiety 2016, 33(10): 939-959.
[34]
Zhou C, Zhang H, Qin Y, et al. A systematic review and meta-analysis of deep brain stimulation in treatment- resistant depression. Prog Neuropsychopharmacol Biol Psychiatry 2018, 82: 224-232.
Publication history
Copyright
Rights and permissions

Publication history

Received: 10 January 2022
Revised: 22 February 2022
Accepted: 23 February 2022
Published: 01 April 2022
Issue date: March 2022

Copyright

© The authors 2022.

Rights and permissions

This article is published with open access at www.sciopen.com/journal/2324-2426, distributed under the terms of Creative Commons Attribution 4.0 International License (CC BY).

Return