Abstract
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive–compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC.
Highlights
Deep brain stimulation (DBS) of the nucleus accumbens (NAc), ventral striatum/ventral capsule and the anterior internal capsule (IC) has proven to be an effective treatment for therapy-refractory obsessive–compulsive disorder (OCD).[1,2,3] Clinical observations show that in particular anxiety symptoms decrease rapidly with stimulation.[1,2,3] Interestingly, our clinical observations show that reduction of anxiety in OCD patients is restricted to the symptomatic fear associated with their obsessions and is not related to unconditioned anxiety or general anxiety, suggesting a focused effect of DBS on conditioned anxiety
We examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU))
This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC
Summary
Deep brain stimulation (DBS) of the nucleus accumbens (NAc), ventral striatum/ventral capsule and the anterior internal capsule (IC) has proven to be an effective treatment for therapy-refractory obsessive–compulsive disorder (OCD).[1,2,3] Clinical observations show that in particular anxiety symptoms decrease rapidly with stimulation.[1,2,3] Interestingly, our clinical observations show that reduction of anxiety in OCD patients is restricted to the symptomatic fear associated with their obsessions and is not related to unconditioned anxiety (innate fears) or general anxiety, suggesting a focused effect of DBS on conditioned anxiety (learned fear). This study examines the effect of stimulation in five brain areas (NAc core and shell, the bed nucleus of the stria terminalis (BNST), the IC and the ventral medial caudate nucleus (CAU)). These five brain areas are chosen on grounds of their use in human DBS studies. In the EPM test, a conflict is created between the natural behaviour to explore novel environments and the natural fear of heights and open spaces.[7] Second, we used the Vogel conflict test (VCT), to test for conditioned anxiety, which is based on the conflict that water deprived rats experience when a previously acquired drinking response is ‘punished’ by a mild foot shock.[8] In addition, we used an activity metric to investigate the effect of stimulation on general locomotor behaviour in a novel environment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
