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Introduction: Ecstasy is an amphetamine derivative, which its use has been consistently increasing over the past years. Ecstasy interacts with the glutamatergic system and it is known that glutamate receptors have a key role in learning and memory. The aim of this study was to investigate the interaction of ecstasy and glutamatergic system on learning and memory. Methods: Fifty-six male Wistar rats weighting (250±50 g) were randomly divided into 8 groups, which received injections for 7 consecutive days. Spatial memory was assessed using Morris Water Maze, performed for 5 consecutive days after the treatment period. Results: The swim speed showed no significant difference among the groups. The mean latency time in finding the hidden platform was increased during test trial in the ecstasy, MK-801 (a glutamate antagonist) and ecstasy + MK-801 groups compared to the control (P < 0.05), while it was decreased during test trial in ecstasy, NMDA and ecstasy + NMDA groups compared to the control (P< 0.05). The mean latency distance in finding the hidden platform was increased during test trial in ecstasy, MK-801 and ecstasy + MK-801 groups compared to the control (P < 0.05), and decreased during test trial in ecstasy, NMDA and ecstasy + NMDA groups compared to the control (P<0.05). Conclusion: Results showed that ecstasy with NMDA treatment attenuated the reduced spatial memory by ecstasy. Ecstasy with MK-801 potentiated the reduced spatial memory by ecstasy. [ABSTRACT FROM AUTHOR]