Functional and molecular changes in the nucleus accumbens of MK-801-sensitized rats.
Behav Pharmacol
; 30(5): 383-395, 2019 08.
Article
de En
| MEDLINE
| ID: mdl-30379647
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maléate de dizocilpine
/
Tolérance aux médicaments
/
Noyau accumbens
Limites:
Animals
Langue:
En
Journal:
Behav Pharmacol
Sujet du journal:
CIENCIAS DO COMPORTAMENTO
/
FARMACOLOGIA
Année:
2019
Type de document:
Article