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

Neuropsychopharmacology. 2010 Mar;35(4):1026-39. doi: 10.1038/npp.2009.208. Epub 2010 Jan 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Compulsive Behavior / drug therapy
  • Compulsive Behavior / pathology*
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiopathology*
  • Disease Models, Animal
  • Extinction, Psychological / drug effects
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology
  • GABA Agonists / administration & dosage
  • Male
  • Microinjections / methods
  • Muscimol / administration & dosage
  • Neurotransmitter Agents / metabolism
  • Paroxetine / therapeutic use
  • Prefrontal Cortex / injuries*
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reward
  • Serotonin Uptake Inhibitors / pharmacology
  • Serotonin Uptake Inhibitors / therapeutic use

Substances

  • GABA Agonists
  • Neurotransmitter Agents
  • Serotonin Uptake Inhibitors
  • Muscimol
  • Paroxetine