title: Activity modulation of the globus pallidus and the nucleus entopeduncularis affects compulsive checking in rats.
abstract: Deep brain stimulation at high frequencies (HFS) is currently studied in the treatment of therapy-refractory obsessive-compulsive disorder (OCD). The diversity of targeted brain areas and the discrepancy in demonstrating beneficial effects, highlight the need for better mapping of brain regions in which HFS may yield anti-compulsive effects. This goal may be achieved by investigating the effects of HFS in appropriate animal models of OCD. The present study tested the effect of bilateral HFS or pharmacological inactivation (as induced by intracerebral administration of the GABA-agonist muscimol) of both the Globus pallidus (GP; rodent equivalent to human GP externus) and the Nucleus entopeduncularis (EP; rodent equivalent to human GP internus) on checking behaviour in the quinpirole rat model of OCD. We demonstrate that HFS of the GP does not and HFS of the EP only partially reduces OCD-like behaviour in rats. In contrast, pharmacological inactivation of both GP and EP significantly reduces OCD-like behaviour in the model. These data contrast previously derived data on the effectiveness of HFS of the subthalamic nucleus, nucleus accumbens, GP and EP in the same and other rat models of OCD. We conclude that (i) although GP and EP play an important role in the pathophysiology of OCD, these areas may not represent first choice target structures for HFS, (ii) the effectiveness of HFS may depend on different subtypes of OCD, represented in different animal models, and (iii) differential net mechanisms may subserve the effectiveness of HFS and pharmacological inactivation.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Djodari-Irani
authors.forename: Julia
authors.initials: J
authors.lastname: Klein
authors.forename: Johann
authors.initials: J
authors.lastname: Banzhaf
authors.forename: Daphna
authors.initials: D
authors.lastname: Joel
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Daniel
authors.initials: D
authors.lastname: Harnack
authors.forename: Tobias
authors.initials: T
authors.lastname: Lagemann
authors.forename: Georg
authors.initials: G
authors.lastname: Juckel
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morgenstern
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
mesh_terms: D000818:Animals; D003192:Compulsive Behavior / Q000503:physiopathology* / Q000523:psychology*; D046690:Deep Brain Stimulation; D018491:Dopamine Agonists / Q000494:pharmacology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D020392:Entopeduncular Nucleus / Q000187:drug effects / Q000503:physiopathology*; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018491:Dopamine Agonists; D018755:GABA Agonists; D019257:Quinpirole; D009118:Muscimol