The facilitating effect of MK-801 on inhibitory avoidance memory via mTOR signaling in the mouse hippocampus.
Behav Brain Res
; 389: 112630, 2020 07 01.
Article
in En
| MEDLINE
| ID: mdl-32348869
ABSTRACT
Despite the widespread belief that MK-801 induces memory deficits associated with dementia and schizophrenia in animal models, data regarding the impairing effect of MK-801 on aversive memory have been inconclusive. In this study, we investigated the effect of MK-801 on multiple memory stages of the inhibitory avoidance task, as well as its underlying signaling mechanism in the mouse hippocampus. We successfully replicated a previous finding suggesting that systemic injection of MK-801 impaired memory acquisition, but we observed that an intrahippocampal infusion of MK-801 facilitated the same memory process. We also found that both systemic and intrahippocampal administration of MK-801 facilitated memory consolidation and memory retrieval of the inhibitory avoidance task. We demonstrated that MK-801-induced increases in shock sensitivity and locomotor activity in the pre-training regimen confounded the detrimental effect of MK-801 on memory acquisition, thereby reconciling the inconsistent results in previous studies. In addition, the memory-facilitating effect of MK-801 was found to be dependent on drug dose and shock intensity. We next showed that MK-801 induced a fast-onset increase in the extent of mammalian target of rapamycin (mTOR) phosphorylation in the hippocampus. Finally, we observed that rapamycin, an mTOR inhibitor, blocked both the MK-801-induced increases in phosphorylated mTOR and the facilitating effect of MK-801 on memory consolidation. These results indicate that hippocampal mTOR signaling mediates the facilitating effect of MK-801 on memory consolidation of the inhibitory avoidance task. These findings further imply that MK-801 indeed functions as a memory enhancer and that mTOR signaling serves as a therapeutic target for memory disorders.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Avoidance Learning
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Dizocilpine Maleate
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Excitatory Amino Acid Antagonists
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TOR Serine-Threonine Kinases
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Hippocampus
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Memory
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Behav Brain Res
Year:
2020
Document type:
Article
Affiliation country: