DL-AP5 is the racemic form of a selective N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant effects.

DL-AP5, a competitive NMDAR antagonist, on tramadol state-dependent memory.?A single-trial step-down passive avoidance task was used for the assessment of memory retrieval in adult male NMRI mice.?Post-training i.p. administration of an atypical μ-opioid receptor agonist, tramadol (2.5 and 5 mg/kg), dose-dependently induced impairment of memory retention.?Pre-test injection of tramadol (2.5 and 5 mg/kg) induced state-dependent retrieval of the memory acquired under post-training administration of tramadol (5 mg/kg) influence.?Pre-test intra-CA1 injection of NMDA (10-5 and 10-4 μg/mouse) 5 min before the administration of tramadol (5 mg/kg, i.p.) dose-dependently inhibited tramadol state-dependent memory.?Pre-test intra-CA1 injection of DL-AP5 (0.25 and 0.5 μg/mouse) reversed the memory impairment induced by post-training administration of tramadol (5 mg/kg).?Pre-test administration of DL-AP5 (0.25 and 0.5 μg/mouse) with an ineffective dose of tramadol (1.25 mg/kg) restored the retrieval and induced tramadol state-dependent memory.?It can be concluded that dorsal hippocampal NMDAR mechanisms play an important role in the modulation of tramadol state-dependent memory.