Bryce Laver1, Mustansir Diwan1, José N Nobrega1, Clement Hamani2. 1. Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8. 2. 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.
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. LIMITATIONS: 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.
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. LIMITATIONS: 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: Helen S Mayberg; Andres M Lozano; Valerie Voon; Heather E McNeely; David Seminowicz; Clement Hamani; Jason M Schwalb; Sidney H Kennedy Journal: Neuron Date: 2005-03-03 Impact factor: 17.173
Authors: Sidney H Kennedy; Peter Giacobbe; Sakina J Rizvi; Franca M Placenza; Yasunori Nishikawa; Helen S Mayberg; Andres M Lozano Journal: Am J Psychiatry Date: 2011-02-01 Impact factor: 18.112
Authors: Clement Hamani; Mustansir Diwan; Silvia Isabella; Andres M Lozano; José N Nobrega Journal: J Psychiatr Res Date: 2010-01-22 Impact factor: 4.791
Authors: Paul E Holtzheimer; Mary E Kelley; Robert E Gross; Megan M Filkowski; Steven J Garlow; Andrea Barrocas; Dylan Wint; Margaret C Craighead; Julie Kozarsky; Ronald Chismar; Jared L Moreines; Klaus Mewes; Patricio Riva Posse; David A Gutman; Helen S Mayberg Journal: Arch Gen Psychiatry Date: 2012-01-02