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


OBJECTIVE
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.
Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
Noa
N
Albelda
Nitza
N
Bar-On
Daphna
D
Joel
D000818:Animals; D003523:Cycloserine / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003523:Cycloserine