title: Neuroplasticity-dependent and -independent mechanisms of chronic deep brain stimulation in stressed rats.
abstract: Chronic ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) improves depressive-like behaviour in rats via serotonergic and neurotrophic-related mechanisms. We hypothesise that, in addition to these substrates, DBS-induced increases in hippocampal neurogenesis may also be involved. Our results show that stress-induced behavioural deficits in the sucrose preference test, forced swim test, novelty-suppressed feeding test (NSFT) and elevated plus maze were countered by chronic vmPFC DBS. In addition, stressed rats receiving stimulation had significant increases in hippocampal neurogenesis, PFC and hippocampal brain-derived neurotrophic factor levels. To block neurogenesis, stressed animals given DBS were injected with temozolomide. Such treatment reversed the anxiolytic-like effect of stimulation in the NSFT without significantly affecting performance in other behavioural tests. Taken together, our findings suggest that neuroplastic changes, including neurogenesis, may be involved in specific anxiolytic effects of DBS without affecting its general antidepressant-like response.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: F R
authors.initials: FR
authors.lastname: Bambico
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Bregman
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Diwan
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Darvish-Ghane
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Laver
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: B O
authors.initials: BO
authors.lastname: Amorim
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Covolan
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: J N
authors.initials: JN
authors.lastname: Nobrega
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Hamani
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D008297:Male; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D013315:Stress, Psychological / Q000503:physiopathology* / Q000628:therapy*