The role of NMDA receptors in the signal attenuation rat model of obsessive-compulsive disorder.

Abstract:

RATIONALE:In recent years, an increasing body of evidence points to the involvement of the glutamatergic system and specifically the glutamatergic ionotropic N-methyl-D-aspartate (NMDA) receptor in the pathophysiology of obsessive-compulsive disorder (OCD). OBJECTIVES:To test the role of NMDA receptors in compulsive behavior using the signal attenuation rat model of OCD. In this model, 'compulsive' behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. METHODS:The NMDA antagonist, MK 801 (0.025-0.100 mg/kg) and the partial NMDA agonist, D-cycloserine (3-100 mg/kg) were administered to rats just before assessing their lever-press responding following signal attenuation (Experiments 1 and 2, respectively). Because the effects of signal attenuation are assessed under extinction conditions, drug doses that were effective in Experiments 1 and 2 were also tested in an extinction session of lever-press responding that was not preceded by signal attenuation (Experiment 3). RESULTS:Systemic administration of D: -cycloserine (15 mg/kg) selectively decreased compulsive lever pressing, whereas systemic administration of MK 801 did not affect compulsive lever-pressing but dramatically increased resistance to extinction. CONCLUSIONS:Activation of NMDA receptors may have an anti-compulsive effect in OCD patients.

journal_title

Psychopharmacology

authors

Albelda N,Bar-On N,Joel D

doi

10.1007/s00213-010-1808-9

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

13-24

issue

1

eissn

0033-3158

issn

1432-2072

journal_volume

210

pub_type

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