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The role of calcium-calmodulin-dependent protein kinase II in modulation of spatial memory in morphine sensitized rats

•Morphine-induced spatial memory impairment improved by morphine sensitization.•CamKII inhibition in the hippocampus facilitated memory retention induced by morphine sensitization.•Glutamate NMDA receptor plays a major role in morphine-sensitization memory retrieval. It has been shown that drug addi...

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Published in:Behavioural brain research 2019-02, Vol.359, p.298-303
Main Authors: Sadat-Shirazi, Mitra-Sadat, Ahmadian-Moghadam, Hamid, Khalifeh, Solmaz, Nouri Zadeh-Tehrani, Setareh, Farahmandfar, Maryam, Zarrindast, Mohammad-Reza
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container_title Behavioural brain research
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creator Sadat-Shirazi, Mitra-Sadat
Ahmadian-Moghadam, Hamid
Khalifeh, Solmaz
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Farahmandfar, Maryam
Zarrindast, Mohammad-Reza
description •Morphine-induced spatial memory impairment improved by morphine sensitization.•CamKII inhibition in the hippocampus facilitated memory retention induced by morphine sensitization.•Glutamate NMDA receptor plays a major role in morphine-sensitization memory retrieval. It has been shown that drug addiction and memory system are related but the signaling cascades underlying this interaction is not completely revealed yet. It has been demonstrated that binding of Calcium-calmodulin-dependent protein kinase II (CaMKII) to NMDA receptor is important in the memory process. The main objective of the study was to evaluate the role of CaMKII on the spatial memory of rats which previously were sensitized by morphine. The effect of CaMKII inhibitor (KN-93) on memory changes was investigated by hippocampal microinjection of KN-93 on the morphine-sensitized rats. Also, the role of the NMDA receptor in memory retention by KN-93 on the morphine sensitized rat was investigated with NMDA agonist and antagonist. Sensitization was induced by morphine injection (once daily for 3 days) followed by 5 days free of the drug before the trial phase. For the evaluation of spatial memory, the Morris Water Maze test (MWM) was used. Results showed that pre-trial administration of morphine, induced amnesia in MWM (p 
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It has been shown that drug addiction and memory system are related but the signaling cascades underlying this interaction is not completely revealed yet. It has been demonstrated that binding of Calcium-calmodulin-dependent protein kinase II (CaMKII) to NMDA receptor is important in the memory process. The main objective of the study was to evaluate the role of CaMKII on the spatial memory of rats which previously were sensitized by morphine. The effect of CaMKII inhibitor (KN-93) on memory changes was investigated by hippocampal microinjection of KN-93 on the morphine-sensitized rats. Also, the role of the NMDA receptor in memory retention by KN-93 on the morphine sensitized rat was investigated with NMDA agonist and antagonist. Sensitization was induced by morphine injection (once daily for 3 days) followed by 5 days free of the drug before the trial phase. For the evaluation of spatial memory, the Morris Water Maze test (MWM) was used. Results showed that pre-trial administration of morphine, induced amnesia in MWM (p &lt; 0.05). Also, three days pretreatment with morphine (20 mg/kg) followed by five days washout period, caused to enhance memory retrieval in confront with a pre-trial challenging dose of morphine (5 mg/kg). In addition, KN-93 administration during induction phase in morphine sensitization phenomena facilitated morphine-induced memory retention. In addition, inhibition of the NMDA receptor and KN-93 during the induction phase did not improve memory. However; intra-CA1 co-administration of KN-93 and NMDA during the induction phase of morphine sensitization resulted in improving spatial memory. 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Results showed that pre-trial administration of morphine, induced amnesia in MWM (p &lt; 0.05). Also, three days pretreatment with morphine (20 mg/kg) followed by five days washout period, caused to enhance memory retrieval in confront with a pre-trial challenging dose of morphine (5 mg/kg). In addition, KN-93 administration during induction phase in morphine sensitization phenomena facilitated morphine-induced memory retention. In addition, inhibition of the NMDA receptor and KN-93 during the induction phase did not improve memory. However; intra-CA1 co-administration of KN-93 and NMDA during the induction phase of morphine sensitization resulted in improving spatial memory. 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subjects CAMK II inhibitor
Morphine sensitization
NMDA receptors
Spatial memory
title The role of calcium-calmodulin-dependent protein kinase II in modulation of spatial memory in morphine sensitized rats
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