title: Deep brain stimulation of the dorsal raphe inhibits avoidance and escape reactions and activates forebrain regions related to the modulation of anxiety/panic.
abstract: One of the main neurochemical systems associated with anxiety/panic is the serotonergic system originating from the dorsal raphe nucleus (DR). Previous evidence suggests that the DR is composed of distinct subpopulations of neurons, both morphologically and functionally distinct. It seems that mainly the dorsal region of the DR (DRD) regulates anxiety-related reactions, while lateral wings DR (lwDR) serotonin (5-HT) neurons inhibit panic-related responses. In this study we used the technique of deep brain stimulation (DBS) to investigate the role played by the DRD and lwDR in defense. Male Wistar rats were submitted to high-frequency stimulation (100μA, 100Hz) in one of the two DR regions for 1h and immediately after tested in the avoidance or escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been related to generalized anxiety and panic disorder, respectively. After being submitted to the ETM, animals were placed in an open field for locomotor activity assessment. An additional group of rats was submitted to DBS of the DRD or the lwDR and used for quantification of c-Fos immunoreactive (Fos-ir) neurons in brain regions related to the modulation of defense. Results showed that stimulation of the DRD decreased avoidance latencies, an anxiolytic-like effect. DRD stimulation also led to increases in Fos-ir in the medial amygdala, lateral septum and cingulate cortex. DBS applied to the lwDR increased escape latencies, a panicolytic-like effect. This data highlights the importance of raphe topography and the potential benefit of the DBS technique for the treatment of anxiety-related disorders.
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Wscieklica
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil.
authors.forename: Mariana S C F
authors.initials: MSCF
authors.lastname: Silva
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil.
authors.forename: Jéssica A
authors.initials: JA
authors.lastname: Lemes
authors.affiliation: Behavioral Neuroscience, Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg, Germany.
authors.forename: Liana
authors.initials: L
authors.lastname: Melo-Thomas
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil.
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Céspedes
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil. Electronic address: milenabv@gmail.com.
authors.forename: Milena B
authors.initials: MB
authors.lastname: Viana
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001362:Avoidance Learning / Q000502:physiology*; D046690:Deep Brain Stimulation; D065847:Dorsal Raphe Nucleus / Q000473:pathology / Q000503:physiopathology*; D004924:Escape Reaction / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010200:Panic / Q000502:physiology*; D016548:Prosencephalon / Q000473:pathology / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: Anxiety; Deep brain stimulation; Dorsal raphe subnuclei; Elevated T-maze; Fos immunohistochemistry