title: Augmentative therapies do not potentiate the antidepressant-like effects of deep brain stimulation in rats.
abstract: BACKGROUND
  Clinical trials have shown promising results with the use of subcallosal cingulate gyrus deep brain stimulation (DBS) for treatment-resistant depression. However, strategies to manage patients who do not respond to this therapy have not been explored in detail. In rats, DBS in the ventromedial prefrontal cortex (vmPFC) induces a significant antidepressant-like response in the forced swim test (FST). We have used this test to investigate potential interactions between DBS and clinically used augmentative regimens.
  
  
  METHODS
  Rats undergoing the FST were treated with vmPFC DBS along with different augmentative drugs, namely buspirone, risperidone and pindolol. Locomotor activity was tested in an open field.
  
  
  RESULTS
  DBS induced a significant reduction in immobility scores as compared to saline treated controls. These antidepressant-like effects, however, were not potentiated by the co-administration of buspirone, risperidone or pindolol.
  
  
  CONCLUSIONS
  Despite having good predictive validity, animal models are limited from a translational perspective.
  
  
  CONCLUSIONS
  Our results indicate that that the antidepressant-like effects of vmPFC DBS in the FST are not enhanced by augmentative therapies.
authors.affiliation: Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8.
authors.forename: Bryce
authors.initials: B
authors.lastname: Laver
authors.affiliation: Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8.
authors.forename: Mustansir
authors.initials: M
authors.lastname: Diwan
authors.affiliation: Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8.
authors.forename: José N
authors.initials: JN
authors.lastname: Nobrega
authors.affiliation: Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8; Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8. Electronic address: Clement.Hamani@camh.net.
authors.forename: Clement
authors.initials: C
authors.lastname: Hamani
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002065:Buspirone / Q000627:therapeutic use; D046690:Deep Brain Stimulation / Q000379:methods*; D003863:Depression / Q000628:therapy*; D018492:Dopamine Antagonists / Q000627:therapeutic use; D006179:Gyrus Cinguli / Q000502:physiology; D008297:Male; D010869:Pindolol / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000627:therapeutic use
chemical_list: D018492:Dopamine Antagonists; D010869:Pindolol; D018967:Risperidone; D002065:Buspirone
keywords: Augmentative; Cingulate gyrus; Deep brain stimulation; Depression; Prefrontal cortex
references.citation: Brain Res. 1991 Dec 6;566(1-2):26-39
references.pmid: 1726062
references.citation: Curr Opin Psychiatry. 2009 Jan;22(1):7-12
references.pmid: 19122528
references.citation: Neurosci Biobehav Rev. 2005;29(4-5):547-69
references.pmid: 15893822
references.citation: Biol Psychiatry. 2002 Sep 15;52(6):503-28
references.pmid: 12361666
references.citation: Neuropharmacology. 2010 Jun;58(7):1140-6
references.pmid: 20153341
references.citation: Neuron. 2005 Mar 3;45(5):651-60
references.pmid: 15748841
references.citation: Sci Transl Med. 2012 Jul 11;4(142):142rv8
references.pmid: 22786683
references.citation: Trends Pharmacol Sci. 2002 May;23(5):238-45
references.pmid: 12008002
references.citation: Eur J Pharmacol. 1978 Feb 15;47(4):379-91
references.pmid: 204499
references.citation: Am J Psychiatry. 2011 May;168(5):502-10
references.pmid: 21285143
references.citation: Biol Psychiatry. 2008 Sep 15;64(6):461-7
references.pmid: 18639234
references.citation: Behav Brain Res. 1996;73(1-2):43-6
references.pmid: 8788475
references.citation: J Psychiatr Res. 2010 Aug;44(11):683-7
references.pmid: 20096858
references.citation: Psychopharmacology (Berl). 1995 May;119(1):47-54
references.pmid: 7675949
references.citation: J Neurosurg. 2012 Feb;116(2):315-22
references.pmid: 22098195
references.citation: Eur J Pharmacol. 1999 May 14;372(2):127-34
references.pmid: 10395092
references.citation: Psychopharmacology (Berl). 1995 Sep;121(1):66-72
references.pmid: 8539342
references.citation: Am J Psychiatry. 2012 Dec;169(12):1320-1
references.pmid: 23212066
references.citation: Int J Neuropsychopharmacol. 2004 Dec;7(4):391-9
references.pmid: 15140278
references.citation: Brain Res. 2003 Dec 12;993(1-2):59-71
references.pmid: 14642831
references.citation: Biol Psychiatry. 2010 Jan 15;67(2):117-24
references.pmid: 19819426
references.citation: Psychopharmacology (Berl). 1990;101(4):497-504
references.pmid: 1975107
references.citation: Biol Psychiatry. 2012 Jan 1;71(1):30-5
references.pmid: 22000731
references.citation: Biol Psychiatry. 2012 Dec 1;72(11):916-23
references.pmid: 22748616
references.citation: Clin Pharmacol Ther. 2010 Oct;88(4):559-62
references.pmid: 20720537
references.citation: Arch Gen Psychiatry. 2012 Feb;69(2):150-8
references.pmid: 22213770
references.citation: Nat Neurosci. 2010 Oct;13(10):1161-9
references.pmid: 20877280