Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine.

Journal: Bipolar disorders

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Affiliated Institutions:  Functional Neuromodulation and Novel Therapeutics Laboratory, Asia Pacific Centre for Neuromodulation, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia. Department of Neurologic Surgery, Neural Engineering Laboratories, Mayo Clinic, Rochester, Minnesota, USA. School of Engineering, Deakin University, Geelong, Victoria, Australia. School of Medicine, IMPACT-The Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Deakin University, Geelong, Victoria, Australia. Faillace Department of Psychiatry and Behavioral Sciences, Center for Interventional Psychiatry, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA. Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil.

Abstract summary 

Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD.The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph).Wistar rats were given 14 days of m-amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low-frequency stimulation (LFS) or continuous high-frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field tests and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry.M-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M-amph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc.These results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.

Authors & Co-authors:  Varela Boschen Yates Houghton Blaha Lee Bennet Kouzani Berk Quevedo Valvassori Tye

Study Outcome 

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Citations :  Baldessarini RJ, Salvatore P, Khalsa HM, et al. Morbidity in 303 first‐episode bipolar I disorder patients. Bipolar Disord. 2010;12(3):264‐270.
Authors :  12
Identifiers
Doi : 10.1111/bdi.13423
SSN : 1399-5618
Study Population
Male,Female
Mesh Terms
Other Terms
bipolar disorder;deep brain stimulation;depression;dopamine;mania;methamphetamine;psychiatry
Study Design
Study Approach
Country of Study
Publication Country
Denmark