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

Abstract

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). 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. 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). 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. Activation of NMDA receptors may have an anti-compulsive effect in OCD patients.