L-Dopa restores striatal dopamine level but fails to reverse MPTP-induced memory deficits in rats.
The objective of the present investigation was to test the effects of benserazide/L-dopa treatment in a model of learning and memory deficits associated with early Parkinson's disease. Intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a lesion in the substantia nigra, compact part and a specific loss of dopamine (DA) and its metabolites in the striatum of rats and a memory impairment in the two-way active avoidance task. The administration of benserazide/L-dopa (50 and 200 mg/kg) to the MPTP-lesioned rats restored the striatal level of DA, but did not reverse the MPTP-induced learning and memory impairment. As this treatment caused a large increase of DA levels in extrastriatal brain regions of the MPTP-lesioned animals, this study suggests that benserazide/L-dopa therapy was not effective in improving the observed learning impairment because this treatment appears to tilt the balance between DA levels in the striatum and in the extrastriatal regions, such as frontal cortex and limbic structures, resulting in a cognitive deficit.
Gevaerd
M S
MS
Departamento de Farmacologia, UFSC, Florianópolis, Brazil.
Miyoshi
E
E
Silveira
R
R
Canteras
N S
NS
Takahashi
R N
RN
Da Cunha
C
C
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001545:Benserazide / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000978:Antiparkinson Agents; D015306:Biogenic Monoamines; D015259:Dopamine Agents; D007980:Levodopa; D001545:Benserazide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine