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Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2012 May 29; Vol. 109 (22), pp. 8764-9. Date of Electronic Publication: 2012 May 14. - Publication Year :
- 2012
-
Abstract
- Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD.
- Subjects :
- Animals
Anxiety physiopathology
Anxiety psychology
Basal Ganglia metabolism
Conditioning, Psychological physiology
Extracellular Signal-Regulated MAP Kinases metabolism
Fear psychology
Immunohistochemistry
Male
Memory physiology
Motor Activity physiology
Neuronal Plasticity physiology
Obsessive-Compulsive Disorder physiopathology
Obsessive-Compulsive Disorder psychology
Rats
Rats, Sprague-Dawley
Basal Ganglia physiopathology
Deep Brain Stimulation methods
Extinction, Psychological physiology
Fear physiology
Obsessive-Compulsive Disorder therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 109
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 22586125
- Full Text :
- https://doi.org/10.1073/pnas.1200782109