Deep brain stimulation of the dorsal raphe induces anxiolytic and panicolytic-like effects and alters serotonin immunoreactivity

Author(s)

Lemes, J. A. ; Silva, M. S. C. F. ; Goncalves, B. S. M. ; Cespedes, I. C. ; Viana, M. B.

• Document type: Journal article
• Source: Behavioural Brain Research; v. 449, p. 10-pg., 2023-05-09.

Abstract

Previously we showed that Deep Brain Stimulation (DBS) of the dorsal region (DRD) and of the lateral wings of the dorsal raphe (lwDR) respectively decreases anxiety and panic-like responses in the elevated T-maze (ETM). This study investigates neurobiological alterations which might respond for these behavioral effects. Male Wistar rats were submitted to high-frequency stimulation (100 mu A, 100 Hz) of the DRD or of the lwDR for 1 h, and subsequently tested in the avoidance or escape tasks of the ETM. Since serotonin (5-HT) reuptake inhibitors are first line pharmacological treatment for anxiety disorders, we also tested the effects of chronic fluoxetine administration (10 mg/kg, IP, 21 days) on a separate group of rats. An open field was used for locomotor activity assessment. Additionally, we evaluated c-Fos immunoreactivity (Fos-ir) in serotonergic cells of the dorsal raphe (DR). Results showed that DBS of the DRD decreases avoidance reactions, an anxiolytic-like effect, without altering escape or locomotor activity. Both fluoxetine and DBS of the lwDR decreased escape responses in the ETM, a panicolytic-like effect, without altering avoidance measurements or locomotor activity. While DBS of the DRD decreased double immunostaining in the DRD, DBS of the lwDR increased Fos-ir and double immuno-staining in the DRD and lwDR. Fluoxetine also increased double immunostaining in the lwDR and in the DRV but decreased it in the DRD. These results suggest that both the anxiolytic and panicolytic-like effects of DBS and fluoxetine are related to 5-HT modulation in different subnuclei of the DR. (AU)

• FAPESP's process: 18/10530-0 - THE EFFECTS OF FLUOXETIN AND DEEP BRAIN STIMULATION APPLIED TO DIFFERENT SUBNUCLEI OF THE DORSAL RAPHE ON THE BEHAVIOR OF RATS IN THE ELEVATED T-MAZE AND ON SEROTONERGIC AND GABAERGIC NEUROTRANSMISSION
• Grantee: Mariana Santos Carvalho de Faria Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/14420-5 - Neurochemical identity and electrophysiology of defense neurocircuitries involving specific dorsal raphe subnuclei
• Grantee: Jéssica Alves Lemes
• Support Opportunities: Scholarships in Brazil - Doctorate