Differential Effects of Deep Brain Stimulation of the Internal Capsule and the Striatum on Excessive Grooming in Sapap3 Mutant Mice
| Autor: | Damiaan Denys, Ingo Willuhn, Fabiana Santana-Kragelund, Pol Bech, Matthijs G. P. Feenstra, Guoping Feng, Cindy M. Pinhal, Bastijn J.G. van den Boom, Lizz Fellinger, Ralph Hamelink |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Graduate School, Adult Psychiatry |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Elevated plus maze Obsessive-Compulsive Disorder Internal capsule Deep brain stimulation medicine.medical_treatment Deep Brain Stimulation Stimulation Nerve Tissue Proteins Striatum behavioral disciplines and activities 03 medical and health sciences Mice 0302 clinical medicine Internal Capsule Journal Article medicine Animals Prefrontal cortex Biological Psychiatry business.industry Ventral striatum Grooming nervous system diseases Disease Models Animal 030104 developmental biology medicine.anatomical_structure surgical procedures operative Mechanism of action nervous system Mutation Ventral Striatum Female medicine.symptom business Neuroscience therapeutics 030217 neurology & neurosurgery |
| Zdroj: | Biological Psychiatry, 84, 917-925. Elsevier USA Biological psychiatry, 84(12), 917-925. Elsevier USA |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2018.05.011 |
| Popis: | Background Deep brain stimulation (DBS) is an effective treatment for patients with obsessive-compulsive disorder (OCD) that do not respond to conventional therapies. Although the precise mechanism of action of DBS remains unknown, modulation of activity in corticofugal fibers originating in the prefrontal cortex is thought to underlie its beneficial effects in OCD. Methods To gain more mechanistic insight into DBS in OCD, we used Sapap3 mutant mice. These mice display excessive self-grooming and increased anxiety, both of which are responsive to therapeutic drugs used in OCD patients. We selected two clinically relevant DBS targets through which activity in prefronto-corticofugal fibers may be modulated: the internal capsule (IC) and the dorsal part of the ventral striatum (dVS). Results IC-DBS robustly decreased excessive grooming, whereas dVS-DBS was on average less effective. Grooming was reduced rapidly after IC-DBS onset and reinstated upon DBS offset. Only IC-DBS was associated with increased locomotion. DBS in both targets induced c-Fos expression around the electrode tip and in different regions of the prefrontal cortex. This prefronto-cortical activation was more extensive after IC-DBS, but not associated with behavioral effects. Furthermore, we found that the decline in grooming cannot be attributed to altered locomotor activity and that anxiety, measured on the elevated plus maze, was not affected by DBS. Conclusions DBS in both the IC and dVS reduces compulsive grooming in Sapap3 mutant mice. However, IC stimulation was more effective, but also produced motor activation, even though both DBS targets modulated activity in a similar set of prefrontal cortical fibers. |
| Databáze: | OpenAIRE |
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