Parkinson’s disease

Parkinson’s disease is among the neurodegenerative
diseases for which there is no
treatment proved to be clinically effective to
halt or retard neurodegeneration (1). It results
from the degeneration of dopaminergic
neurons in the substantia nigra pars compacta
(SNc) and, to a lesser extent, in the
retrorubral field and ventral tegmental area

(2,3). Indeed, mesencephalic dopaminergic
cells are among the elements of the basal
ganglia most vulnerable to neurodegeneration
(1,3). Therefore, it is of great interest to
look for neuroprotective compounds for the
treatment of Parkinson’s disease.
6-Hydroxydopamine (6-OHDA) and 1-
methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) cause large or partial loss of dopaminergic
cells, respectively, in the SNc of
rats. Their effects have been studied as models
of the advanced or the early phase of
Parkinson’s disease (4-7). 6-OHDA induces
nigral dopaminergic lesion mainly by generating
reactive oxygen species as a result of
its oxidation. This can occur spontaneously
or be induced by monoamine oxidase or iron
(1,6). MPTP is converted into 1-methyl-4-
phenyl-peridinium (MPP+) by glial monoamine
oxidase B. MPP+ accumulates in SNc
dopaminergic cells and acts mainly by inhibiting
mitochondrial complex I, leading to
a decrease in cellular ATP levels and cell
death (8).
Sodium thiopental and a mixture of ketamine/
xylazine (K/X) have been used to anesthetize
rats during surgery for intracerebral
administration of MPTP or 6-OHDA. In the
present study, we report that lesions of the
SNc (induced by MPTP or 6-OHDA) were
amnestic only when the rats were operated
under thiopental, but not under K/X anesthesia.
The aim of the present investigation was
to study whether the NMDA receptor antagonist,
ketamine, has a neuroprotective
effect on the MPTP and 6-OHDA rat models
of Parkinson’s disease.