fa Behavioral Neuroscience Behavioral Neuroscience Original Original <p style="text-align: justify;"><strong>Introduction:</strong> Activation of N-methyl-d-aspartate (NMDA) glutamate receptors in the nucleus&nbsp;accumbens is a component of drug-induced reward mechanism. In addition, NMDA receptors&nbsp;play a major role in brain reward system and activation of these receptors can change firing&nbsp;pattern of dopamine neurons. Blockade of glutamatergic neurotransmission reduces the&nbsp;expression of conditioned place preference (CPP) induced by morphine. Therefore, in this study,&nbsp;by using an NMDA receptor antagonist, DL-2-Amino-5-phosphonopentanoic acid sodium salt&nbsp;(AP5), the role of NMDA receptors on the maintenance and reinstatement of morphine-CPP was&nbsp;investigated.<br> <strong>Methods: </strong>Forty-three adult male albino Wistar rats were used in this study. After subcutaneous&nbsp;administration of effective dose of morphine (5 mg/kg) during CPP paradigm, the animals&nbsp;received intracerebroventricular doses of AP5(1, 5, and 25 mM/5&mu;L saline) during extinction&nbsp;period (free morphine stage). Conditioning score was recorded during extinction period and&nbsp;reinstatement phase. Besides, another group of the animals received a single dose administration&nbsp;of AP5(5 mM) just before the administration of ineffective dose of morphine (1 mg/kg) in&nbsp;reinstatement phase.<br> <strong>Results:</strong> The results revealed that two doses of this antagonist (5 and 25 mM) significantly&nbsp;shortened the extinction period of morphine-CPP but did not reduce reinstatement induced by&nbsp;priming dose of morphine. Moreover, the single dose administration of AP5(5 mM) just before&nbsp;prime-morphine injection decreased reinstatement of morphine-CPP.<br> <strong>Conclusion: </strong>These findings indicate that blockade of NMDA receptors during extinction period&nbsp;reduces maintenance but not reinstatement of morphine. In addition, blocking these receptors in&nbsp;reinstatement phase decreases reinstatement to extinguished morphine.</p> Reward, Conditioned place preference, NMDA receptor, Morphine maintenance, Reinstatement 341 350 http://bcn.iums.ac.ir/browse.php?a_code=A-10-992-8&slc_lang=fa&sid=1 Ali Siahposht-Khachaki haghparast@yahoo.com 1370031947532846008565 1370031947532846008565 No Department of Physiology and Pharmacology, School of Medicine, Ramsar International Branch, Mazandaran University of Medical Sciences, Sari, Iran. Zahra Fatahi 1370031947532846008566 1370031947532846008566 No Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Abbas Haghparast haghparast@yahoo.com 1370031947532846008567 1370031947532846008567 Yes Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.