title: Behavioral and neurobiological effects of deep brain stimulation in a mouse model of high anxiety- and depression-like behavior.
abstract: Increasing evidence suggests that high-frequency deep brain stimulation of the nucleus accumbens (NAcb-DBS) may represent a novel therapeutic strategy for individuals suffering from treatment-resistant depression, although the underlying mechanisms of action remain largely unknown. In this study, using a unique mouse model of enhanced depression- and anxiety-like behavior (HAB), we investigated behavioral and neurobiological effects of NAcb-DBS. HAB mice either underwent chronic treatment with one of three different selective serotonin reuptake inhibitors (SSRIs) or received NAcb-DBS for 1 h per day for 7 consecutive days. Animals were tested in established paradigms revealing depression- and anxiety-related behaviors. The enhanced depression-like behavior of HAB mice was not influenced by chronic SSRI treatment. In contrast, repeated, but not single, NAcb-DBS induced robust antidepressant and anxiolytic responses in HAB animals, while these behaviors remained unaffected in normal depression/anxiety animals (NAB), suggesting a preferential effect of NAcb-DBS on pathophysiologically deranged systems. NAcb-DBS caused a modulation of challenge-induced activity in various stress- and depression-related brain regions, including an increase in c-Fos expression in the dentate gyrus of the hippocampus and enhanced hippocampal neurogenesis in HABs. Taken together, these findings show that the normalization of the pathophysiologically enhanced, SSRI-insensitive depression-like behavior by repeated NAcb-DBS was associated with the reversal of reported aberrant brain activity and impaired adult neurogenesis in HAB mice, indicating that NAcb-DBS affects neuronal activity as well as plasticity in a defined, mood-associated network. Thus, HAB mice may represent a clinically relevant model for elucidating the neurobiological correlates of NAcb-DBS.
authors: Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors: Claudia
authors: C
authors: Schmuckermair
authors: Stefano
authors: S
authors: Gaburro
authors: Anupam
authors: A
authors: Sah
authors: Rainer
authors: R
authors: Landgraf
authors: Simone B
authors: SB
authors: Sartori
authors: Nicolas
authors: N
authors: Singewald
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000628:therapy*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D046690:Deep Brain Stimulation; D018891:Dentate Gyrus / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000628:therapy*; D006624:Hippocampus / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D055495:Neurogenesis / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*
chemical_list: D000928:Antidepressive Agents