The Effect of the Blockage of the Receptors of Glutamate N-Methyl-D-Aspartate (Nmda) in Prefrontal Cortex on Morphine Tendency in Male Rat



Javadi S^{1, 2, 4} ; Alaei H³ ; Hosseini SE^{2, 4} ; Edalatmanesh MA^{2, 4} ; Radahmadi M³ Show Affiliations
Source: Journal of Isfahan Medical School Published:2016

Abstract

Background: Addiction is a brain disorder associated with neurobiologic changes. Medial prefrontal cortex (mPFC) plays an important role in learning, memory, reward system and addiction processes. Present study investigated the effect of 2-amino-5-phosphopentanoic acid (AP5), glutamate receptor antagonist, on morphine tendency. Methods: We used 27 groups (n = 6) of male Wistar rats; 7 groups were used for determining the effective and ineffective doses of morphine and 20 experimental groups also were used for studying the effect of various doses of AP5 on morphine tendency in acquisition and expression phases of conditioned place preference (CPP) paradigm; then, CPP index was calculated. Findings: Doses of 2.5, 5, 7.5 and 10 mg/kg of morphine significantly increased CPP index in morphine groups compared to saline group (P < 0.050, P < 0.001, P < 0.010 and P < 0.001, respectively) but, in doses of 0.5 and 1 mg/kg of morphine, the changes were not significant. Microinjection of different doses of AP5 into the prefrontal cortex with injection of the effective dose of morphine significantly reduced the acquisition and the expression phases of CPP in test groups compared to the sham group, while the ineffective dose of morphine reduced the expression phase of CPP paradigm (P < 0.001) and did not have significant effect on the acquisition phase of CPP. Conclusion: It seems that microinjection of AP5 into the prefrontal cortex reduces CPP index and consequently morphine tendency; these may be due to the impairment of learning and dysfunction of reward-related memory in response to morphine. © 2016, Isfahan University of Medical Sciences(IUMS). All rights reserved.