Roger B. Varela, Suelen L. Boschen, Nathanael Yates, Tristan Houghton, Charles D. Blaha, Kendall H. Lee, Kevin E. Bennet, Abbas Z. Kouzani, Michael Berk, João Quevedo, Samira S. Valvassori, Susannah J. Tye
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引用次数: 0
Abstract
Background
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.
Aim
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).
Methods
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.
Results
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.
Conclusion
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.
期刊介绍：
Bipolar Disorders is an international journal that publishes all research of relevance for the basic mechanisms, clinical aspects, or treatment of bipolar disorders and related illnesses. It intends to provide a single international outlet for new research in this area and covers research in the following areas:
biochemistry
physiology
neuropsychopharmacology
neuroanatomy
neuropathology
genetics
brain imaging
epidemiology
phenomenology
clinical aspects
and therapeutics of bipolar disorders
Bipolar Disorders also contains papers that form the development of new therapeutic strategies for these disorders as well as papers on the topics of schizoaffective disorders, and depressive disorders as these can be cyclic disorders with areas of overlap with bipolar disorders.
The journal will consider for publication submissions within the domain of: Perspectives, Research Articles, Correspondence, Clinical Corner, and Reflections. Within these there are a number of types of articles: invited editorials, debates, review articles, original articles, commentaries, letters to the editors, clinical conundrums, clinical curiosities, clinical care, and musings.
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