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

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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.

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  1. Department of Psychology, Tel Aviv University, Tel Aviv, Israel

    Noa Albelda, Nitza Bar-On & Daphna Joel

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  1. Noa Albelda
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  2. Nitza Bar-On
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  3. Daphna Joel
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Correspondence to Daphna Joel.

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Albelda, N., Bar-On, N. & Joel, D. The role of NMDA receptors in the signal attenuation rat model of obsessive–compulsive disorder. Psychopharmacology 210, 13–24 (2010). https://doi.org/10.1007/s00213-010-1808-9

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  • DOI: https://doi.org/10.1007/s00213-010-1808-9

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