The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities.
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.
Da Cunha
Claudio
C
Laboratório de Fisiologia e Farmacologia do SNC, Departamento de Farmacologia, UFPR, Curitiba, PR, Brazil. dacunha@bio.ufpr.br
Angelucci
Miriam Elizabeth Mendes
ME
Canteras
Newton S
NS
Wonnacott
Susan
S
Takahashi
Reinaldo N
RN
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
D011954:Receptors, Dopamine; D018047:Receptors, Purinergic P1; D002110:Caffeine; D007980:Levodopa