The role of the striatum in compulsive behavior in intact and orbitofrontal-cortex-lesioned rats: Possible involvement of the serotonergic system

Eduardo A. Schilman, Oded Klavir, Christine Winter, Reinhard Sohr, Daphna Joel

Research output: Contribution to journalArticlepeer-review

Abstract

In the signal attenuation rat model of obsessive-compulsive disorder (OCD), compulsive behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. We have recently found that lesions to the rat orbitofrontal cortex (OFC) led to an increase in compulsive lever-pressing that was prevented by systemic administration of the selective serotonin reuptake inhibitor paroxetine, and paralleled by an increase in the density of the striatal serotonin transporter. This study further explored the interaction between the OFC, the striatum, and the serotonergic system in the production of compulsive lever-pressing. Experiment 1 revealed that OFC lesions decrease the content of serotonin, dopamine, glutamate, and GABA in the striatum. Experiment 2 showed that intrastriatal administration of paroxetine blocked OFC lesion-induced increased compulsivity, but did not affect compulsive responding in intact rats. Experiments 3 and 4 found that pre-training striatal lesions had no effect on compulsive lever-pressing, whereas post-training striatal inactivation exerted an anticompulsive effect. These results strongly implicate the striatum in the expression of compulsive lever-pressing in both intact and OFC-lesioned rats. Furthermore, the results support the possibility that in a subpopulation of OCD patients a primary pathology of the OFC leads to a dysregulation of the striatal serotonergic system, which is manifested in compulsive behavior, and that antiobsessional/anticompulsive drugs exerts their effects, in these patients, by normalizing the dysfunctional striatal serotonergic system.

Original languageEnglish
Pages (from-to)1026-1039
Number of pages14
JournalNeuropsychopharmacology
Volume35
Issue number4
DOIs
StatePublished - Mar 2010
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institute for Psychobiology in IsraelFFounded by the Charles E Smith Family (Grant no. 2004-5-13) and by the Israel Science Foundation (Grant no. 942/01-1).

Keywords

  • Caudate-putamen
  • Extinction
  • Inactivation
  • Paroxetine
  • Signal attenuation

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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