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Effects of MK-801 on recognition and neurodegeneration in an MPTP-induced Parkinson's rat model.
- Source :
-
Behavioural brain research [Behav Brain Res] 2012 Apr 01; Vol. 229 (1), pp. 41-7. Date of Electronic Publication: 2012 Jan 02. - Publication Year :
- 2012
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Abstract
- Several years after the diagnosis of Parkinson's disease (PD), 20-30% of PD patients develop dementia, known as Parkinson's disease dementia (PDD), the features of which include impairment of short-term memory and recognition function. Hyperactivation of the glutamatergic system is implicated in the neurodegeneration seen in PD. The aim of this study was to determine the effects of MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, on short-term memory and object recognition in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat animal model. MPTP was injected stereotaxically into the substantia nigra pars compacta (SNc) of male Wistar rats, then, starting 1 day later (day 1), the rats were injected daily with MK-801 (0.2 mg/kg/day, i.p.) and rats underwent a bar test on days 1-7, a T-maze test on days 8-10, and object recognition test on days 12-14. On day 1, the animals showed motor dysfunction, which recovered to control levels on day 7. MPTP-lesioned rats showed impairment of working memory in the T-maze test and of recognition in the object recognition test, both of which were prevented by MK-801 treatment. Furthermore, MPTP lesion-induced dopaminergic degeneration in the nigrostriatal system, microglial activation in the SNc, and cell loss in the hippocampal CA1 area were all improved by MK-801 treatment. These results suggest that NMDA receptors are involved in PD-related neuronal and behavioral dysfunction.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration & dosage
Analysis of Variance
Animals
Brain drug effects
Brain metabolism
Brain pathology
Disease Models, Animal
Gene Expression Regulation drug effects
MPTP Poisoning complications
MPTP Poisoning pathology
Male
Maze Learning drug effects
Memory Disorders etiology
Memory Disorders pathology
Neurodegenerative Diseases etiology
Neurodegenerative Diseases pathology
Rats
Rats, Wistar
Time Factors
Tyrosine 3-Monooxygenase metabolism
Dizocilpine Maleate therapeutic use
Memory Disorders drug therapy
Neurodegenerative Diseases drug therapy
Neuroprotective Agents therapeutic use
Recognition, Psychology drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7549
- Volume :
- 229
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Behavioural brain research
- Publication Type :
- Academic Journal
- Accession number :
- 22227506
- Full Text :
- https://doi.org/10.1016/j.bbr.2011.12.035