Abstract
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.
Keywords
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Article info
Publication history
Published online: May 23, 2018
Accepted:
May 2,
2018
Received in revised form:
May 2,
2018
Received:
March 22,
2017
Identification
Copyright
© 2018 Society of Biological Psychiatry.
