The involvement of dorsal hippocampus in dextromethorphan-induced state-dependent learning in mice

In an effort to understand the effect of dextromethorphan (DM; 3-methoxy-17-methylmorphinan), a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptors on memory retrieval, male NMRI mice received intraperitoneal (i.p.) or intra-CA1 injection of this drug before or after training and before testing in passive avoidance task. Pre-training i.p. (20mg/kg) or intra-CA1 (0.5 and 1μg/mouse) administration of DM induced amnesia in a dose-dependent manner. Post-training i.p. (10 and 20mg/kg) or intra-CA administration of DM (0.5 and 1μg/mouse) however, did not affect the memory retrieval. Moreover, memory retrieval was impaired in animals receiving either i.p. (20mg/kg) or intra-CA1 administration of DM (0.5 and 1μg/mouse) prior to testing, suggesting the DM-induced amnesia. Interestingly, the amnestic effect of pre-training i.p. (20mg/kg) or intra-CA1 administration of DM (1μg/mouse) was restored in mice receiving pre-test i.p. (5 and 10mg/kg) or intra-CA1 (0.25 and 0.5μg/mouse) administration of the drug, indicating DM-induced state-dependent learning. Taken together, it can be concluded that DM administration impairs memory retrieval in a dose- and time-dependent manner. Moreover, DM can induce state-dependent learning. Dorsal hippocampus appears to play an important role upon DM influence of learning and memory processes. •Pre-training or pre-test i.p. injection of DM induced memory impairment.•Pre-training or pre-test intra-CA1 injection of DM induced memory impairment.•I.p. or intra-CA1 injection of DM can also induce state-dependent learning.•Dorsal hippocampus has an important role upon DM effect on learning and memory.