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Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

Kim, Y., McGee, S., Czeczor, J.K., Walker, A.J., Kale, R.P., Kouzani, A.Z., Walder, K., Berk, M. and Tye, S.J. 2016, Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects, Translational psychiatry, vol. 6, Article number : e842, pp. 1-7, doi: 10.1038/tp.2016.84.

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Title Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects
Author(s) Kim, Y.
McGee, S.
Czeczor, J.K.
Walker, A.J.
Kale, R.P.
Kouzani, A.Z.
Walder, K.
Berk, M.ORCID iD for Berk, M. orcid.org/0000-0002-5554-6946
Tye, S.J.
Journal name Translational psychiatry
Volume number 6
Season Article number : e842
Start page 1
End page 7
Total pages 7
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2016
ISSN 2158-3188
Summary Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg(-1)) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation.
Language eng
DOI 10.1038/tp.2016.84
Field of Research 170199 Psychology not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30085930

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.