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- W2898850528 abstract "Behavioural sensitization is a putative mechanism in the pathophysiology of drug addiction and neuropsychiatric disorders such as schizophrenia. In rodents, drug-induced behavioural sensitization has been described for several different drug classes. The N-methyl-d-aspartate receptor antagonist MK-801 can inhibit sensitization to other drugs of abuse. However, MK-801 also produces behavioural sensitization to its own hyperlocomotor inducing effects, suggesting that MK-801 sensitization has a distinctive mechanism of action. The aim of this study was to carry out a functional and molecular analysis of the nucleus accumbens (NAc) of adult male Sprague-Dawley rats sensitized to MK-801 (seven daily injections of 0.25 mg/kg, 5 days of withdrawal and subsequent 0.25 mg/kg challenge), or following acute MK-801 (0.25 mg/kg), or naive rats as controls. Locomotor activity was the primary measure of sensitization. Ex-vivo slice electrophysiology showed a decrease in the excitatory synaptic strength in the NAc of rats sensitized to MK-801 compared with acute MK-801 treatment or naive controls. An LC–MS/MS SWATH proteomics approach showed that proteins altered by MK-801 sensitization were predominantly related to functions including calcium and glutamate signalling, and mitochondrial dysfunction. These results shed some light on neural changes in the NAc after sensitization to MK-801. This model could prove useful for studying the role of N-methyl-d-aspartate receptors in the pathophysiology of drug addiction and schizophrenia." @default.
- W2898850528 created "2018-11-09" @default.
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- W2898850528 date "2019-08-01" @default.
- W2898850528 modified "2023-09-23" @default.
- W2898850528 title "Functional and molecular changes in the nucleus accumbens of MK-801-sensitized rats" @default.
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- W2898850528 doi "https://doi.org/10.1097/fbp.0000000000000447" @default.
- W2898850528 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30379647" @default.
- W2898850528 hasPublicationYear "2019" @default.
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