title: Reduction of the Morphine Maintenance by Blockade of the NMDA Receptors during Extinction Period in Conditioned Place Preference Paradigm of Rats.
abstract: BACKGROUND
  Activation of N-methyl-d-aspartate (NMDA) glutamate receptors in the nucleus accumbens is a component of drug-induced reward mechanism. In addition, NMDA receptors play a major role in brain reward system and activation of these receptors can change firing pattern of dopamine neurons. Blockade of glutamatergic neurotransmission reduces the expression of conditioned place preference (CPP) induced by morphine. Therefore, in this study, by using an NMDA receptor antagonist, DL-2-Amino-5-phosphonopentanoic acid sodium salt (AP5), the role of NMDA receptors on the maintenance and reinstatement of morphine-CPP was investigated.
  
  
  METHODS
  Forty-three adult male albino Wistar rats were used in this study. After subcutaneous administration of effective dose of morphine (5 mg/kg) during CPP paradigm, the animals received intracerebroventricular doses of AP5(1, 5, and 25 mM/5μL saline) during extinction period (free morphine stage). Conditioning score was recorded during extinction period and reinstatement phase. Besides, another group of the animals received a single dose administration of AP5(5 mM) just before the administration of ineffective dose of morphine (1 mg/kg) in reinstatement phase.
  
  
  RESULTS
  The results revealed that two doses of this antagonist (5 and 25 mM) significantly shortened the extinction period of morphine-CPP but did not reduce reinstatement induced by priming dose of morphine. Moreover, the single dose administration of AP5(5 mM) just before prime-morphine injection decreased reinstatement of morphine-CPP.
  
  
  CONCLUSIONS
  These findings indicate that blockade of NMDA receptors during extinction period reduces maintenance but not reinstatement of morphine. In addition, blocking these receptors in reinstatement phase decreases reinstatement to extinguished morphine.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Ramsar International Branch, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Siahposht-Khachaki
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fatahi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
keywords: Conditioned place preference; Morphine maintenance; NMDA receptor; Reinstatement; Reward