The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities

C Da Cunha, M E M Angelucci, N S Canteras, S Wonnacott, R N Takahashi

Research output: Contribution to journalArticle

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Abstract

1. In this article we review the studies of memory disabilities in a rat model of Parkinson's disease (PD).
2. Intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rats causes a partial lesion in the substantia nigra, compact part (SNc) and a specific loss of dopamine and its metabolites in the striatum of rats.
3. These animals present learning and memory deficits but no sensorimotor impairments, thus modeling the early phase of PD when cognitive impairments are observed but the motor symptoms of the disease are barely present.
4. The cognitive deficits observed in these animals affect memory tasks proposed to model habit learning (the cued version of the water maze task and the two-way active avoidance task) and working memory (a working memory version of the water maze), but spare long-term spatial memory (the spatial reference version of the Morris water maze).
5. The treatment of these animals with levodopa in a dose that restores the striatal level of dopamine does not reverse these memory impairments, probably because this treatment promotes a high level of dopamine in extrastriatal brain regions, such as the prefrontal cortex and the hippocampus.
6. On the other hand, the adenosine receptor antagonist, caffeine, partly reverse the memory impairment effect of SNc lesion in these rats. This effect may be due to caffeine action on nigrostriatal neurons, since it induces dopamine release and modulates the interaction between adenosine and dopamine receptor activity.
7. These results suggest that the MPTP SNc-lesioned rats are a good model to study memory disabilities related to PD and that caffeine and other selective A( 2A) adenosine receptor antagonists are promising drugs to treat this symptoms in PD patients.
Original languageEnglish
Pages (from-to)227-237
Number of pages11
JournalCellular and Molecular Neurobiology
Volume22
Issue number3
DOIs
Publication statusPublished - 2002

Fingerprint

Dopaminergic Neurons
Parkinson Disease
Dopamine
Substantia Nigra
Caffeine
Purinergic P1 Receptor Antagonists
Short-Term Memory
Water
Learning
Corpus Striatum
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Purinergic P1 Receptors
Long-Term Memory
Memory Disorders
Dopamine Receptors
Levodopa
Prefrontal Cortex
Habits
Hippocampus
Pars Compacta

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The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities. / Da Cunha, C; Angelucci, M E M; Canteras, N S; Wonnacott, S; Takahashi, R N.

In: Cellular and Molecular Neurobiology, Vol. 22, No. 3, 2002, p. 227-237.

Research output: Contribution to journalArticle

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