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The involvement of dorsal hippocampus in dextromethorphan-induced state-dependent learning in mice
Mohammad-Reza Zarrindast1, Vahid Ownegh2, Ameneh Rezayof3
1Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran; Institute of Cognitive Science Studies (ICSS), Tehran, Iran.
Abstract:
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 1 μg/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 1 μg/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 1 μg/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 (1 μg/mouse) was restored in mice receiving pre-test i.p. (5 and 10mg/kg) or intra-CA1 (0.25 and 0.5 μg/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.
Insights
Dextromethorphan (DM) impairs memory retrieval when given before training or testing, but not after. This drug also causes state-dependent learning, where memory is only accessible when DM is present.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- N-methyl-d-aspartate (NMDA) receptors are crucial for learning and memory.
- Dextromethorphan (DM) is a noncompetitive NMDA receptor antagonist.
Purpose of the Study:
- To investigate the effects of dextromethorphan (DM) on memory retrieval.
- To determine the role of the dorsal hippocampus in DM-induced memory impairment.
Main Methods:
- Male NMRI mice were used in a passive avoidance task.
- Dextromethorphan (DM) was administered intraperitoneally (i.p.) or intra-CA1 before training, after training, or before testing.
- Memory retrieval was assessed at different time points post-administration.
Main Results:
- Pre-training administration of DM induced amnesia in a dose-dependent manner.
- Post-training administration of DM did not affect memory retrieval.
- Pre-test administration of DM impaired memory retrieval, indicating DM-induced amnesia.
- DM administration also induced state-dependent learning, where memory recall was facilitated by the presence of DM.
Conclusions:
- Dextromethorphan (DM) impairs memory retrieval in a dose- and time-dependent manner.
- DM can induce state-dependent learning.
- The dorsal hippocampus plays a significant role in DM's effects on learning and memory processes.
