Mood regulatory actions of nucleus accumbens deep brain stimulation Kale, R., Kouzani, A., Frye, M., Walder, K., Berk, M. and Tye, S. 2015, Mood regulatory actions of nucleus accumbens deep brain stimulation, in ISBD 2015: Proceedings of the 17th Annual Conference of the International Society for Bipolar Disorders, Wiley, Hoboken. N.J., pp. 57-57, doi: 10.1111/bdi.12308. Attached Files Name Description MIMEType Size Downloads Title Mood regulatory actions of nucleus accumbens deep brain stimulation Author(s) Kale, R. Kouzani, A. orcid.org/0000-0002-6292-1214 Frye, M. Walder, K. orcid.org/0000-0002-6758-4763 Berk, M. orcid.org/0000-0002-5554-6946 Tye, S. Conference name International Society for Bipolar Disorders. Annual Conference (17th : 2015 : Toronto, Canada) Conference location Toronto, Canada Conference dates 3-6 Jun 2015 Title of proceedings ISBD 2015: Proceedings of the 17th Annual Conference of the International Society for Bipolar Disorders Publication date 2015 Start page 57 End page 57 Total pages 1 Publisher Wiley Place of publication Hoboken. N.J. Keyword(s) Science & Technology Life Sciences & Biomedicine Clinical Neurology Neurosciences Psychiatry Neurosciences & Neurology Summary The mood regulatory mechanisms of deep brain stimulation (DBS)therapy are yet to be fully understood. DBS is shown to have antidepressant actions in severe, treatment-resistant depression (TRD).Interestingly, DBS of mesoaccumbens neurologic targets, includingthe nucleus accumbens (NAc), have also been shown to induce mania in vulnerable individuals. The nucleus accumbens (NAc) is a critical node in the mesocorticolimbic system and plays a major role in mediating antidepressant behavioral responses in the forced swim test (FST), a preclinical screen for antidepressant efficacy. This study investigates the antidepressant effects of NAc DBS in an established animal model of TRD. Wistar rats were divided into 4 groups: TRD-DBS (n = 9), TRD-Sham (n = 8), TRD (n = 10), and Control (n = 10). Bilateral stimulating electrodes were implanted into the NAc of TRD-Sham and TRD-DBS animals. Antidepressant-resistance and depression behaviors were induced through adrenocorticotropic-hormone (ACTH-(1–24); 100 lg/day; 2nd and 3rd weeks) administration and concurrent social isolation (all 3 weeks) respectively. DBS was administered throughout the 2nd week of ACTH treatment via a back mounted rodent DBS system. 24-hour locomotor activity counts were obtained using infrareddetectors and weekly sucrose preference tests were performedthroughout the 3 week protocol. Open field and FST were completedat the end of the 3 weeks. Brains were then removed and stored at 80°C. NAc tissue levels of brain-derived and glialderived neurotrophic factors (BDNF and GDNF, respectively) were quantified using western blot. Results demonstrate significant increases in locomotor activity for TRD-DBS animals (DBS-Vs-Sham: p = 0.0248). Lowered immobility was observed during FST for TRD-DBS animals (DBS-Vs-Sham: p = 0.0188). ACTHinduced BDNF expression increased in the outer region substructure NAc-shell (p = 0.0487) and decreased in the inner region substructure NAc-core (p = 0.0275) compared to controls. These datasupport antidepressant actions of NAc DBS in TRD. Local changes in neurotrophic factors may contribute to these mechanisms. Importantly, observed increases in locomotor activity over the 3 weeks highlight the potential for mesoaccumbens DBS to impact behaviors such as locomotor activity which may contribute to risk for induction of mania. Preliminary analysis of concurrent effects of daily dopamine reuptake inhibitor GBR12909 (16 mg/kg) administration coupled with NAc DBS demonstrates dopamine-mediated augmentation of these mania-like behaviors. Notes Published in Bipolar Disorders, 17 (Suppl. 1) 49–57 ISSN 1398-5647 Language eng DOI 10.1111/bdi.12308 Field of Research 110319 Psychiatry (incl Psychotherapy) Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences HERDC Research category E3.1 Extract of paper Copyright notice ©2015, The Authors Persistent URL http://hdl.handle.net/10536/DRO/DU:30074299 Document type: Conference Paper Collections: School of Medicine School of Engineering Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. 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