Water maze test

Water maze test

The differences of working memory between
thiopental and K/X anesthetized animals
also suggest a neuroprotective effect of
the latter anesthetic. The data in Figure 4A
and B are shown in different graphics, in
order to facilitate comparison of the neuroprotective
effects of the anesthetics, but the
data of all groups were analyzed together.
As can be seen, MPTP- and 6-OHDA-lesioned
animals presented worse scores in the
water maze task compared to control animals
only after being operated under thiopental
anesthesia (F(4,71) = 5.13, P ≤ 0.001,
two-way ANOVA, treatment factor; P ≤ 0.05
Newman-Keuls test). The MPTP- and 6-
OHDA-lesioned animals operated under thiopental
anesthesia also traveled longer distances
to find the hidden platform in the
water maze (data not shown; F(4,71) = 5.13,
P ≤ 0.001, two-way ANOVA, treatment factor;
P ≤ 0.05, Newman-Keuls test). The average
swimming speed of all groups tested
was equivalent (F(4,71) = 0.07, P > 0.2,
ANOVA).
Discussion
The present results suggest that anesthesia
with K/X protected the SNc against lesions
induced by 6-OHDA and MPTP. This
neuroprotective effect was observed at the
level of nigral TH-immunoreactive neurons,
striatal dopamine and DOPAC tissue concentration,
and for behavioral performance
of the animals in a test sensitive to changes
in the nigrostriatal pathway. One exception
was observed regarding striatal dopamine
depletion when the lesion was induced with
MPTP. Since MPTP caused a more modest
depletion of dopamine compared to 6-
OHDA, it is possible that the neuroprotective
effect of K/X was more evident in the
latter case.
The blockade of NMDA receptors by
ketamine is a possible mechanism whereby
the K/X mixture protected SNc neurons
against the MPTP insult since neuroprotection
of SNc cells against the MPTP or MPP+
insult by NMDA receptor antagonists has
been reported (11-14). However, the noncompetitive
NMDA receptor antagonist,
MK-801, failed to protect rats against MPP+
and mice against MPTP neurotoxicity (15-
17). The observed neuroprotective effect of
ketamine may also be mediated by its dopamine
D2 receptor agonist action, as is the
case for other agonists such as pramipexole
reported to be neuroprotective against MPTP
and 6-OHDA lesions (18).
Alternatively, ketamine has been reported
to act as an inhibitor of 6-OHDA uptake and
as a scavenger of free radicals in dopaminergic
neurons. Datla and co-workers (19) have
shown that higher doses of 6-OHDA (10 μg)
were necessary to provoke significant depletion
of SNc TH-immunostained cells and
dopaminergic depletion in the rat.
The neuroprotective effect of K/X was
sufficient to prevent working memory impairment
caused by both MPTP and 6-OHDA

lesions. This result probably was not due to
a motor impairment since, at the time of this
test, the animals swam normally and the
latency to find the platform in the first trial of
the first training day (F(4,71) = 0.10, P > 0.2,
ANOVA) and the mean swimming speed
(F(4,71) = 0.07, P > 0.2, ANOVA) did not
differ significantly between groups (20).
The percentages of loss of TH-immunostained
cells and striatal dopamine in the
same animals were not similar. It is possible
that the surviving SNc cells increased the
synthesis and/or release of dopamine in the
striatum. During the early stages of the disease,
the remaining cells maintain nigrostriatal
function at normal physiological levels.
For this reason, Parkinson’s disease patients
start to develop motor symptoms only
when almost 75% of their dopaminergic nigrostriatal
neurons have died.
Cognitive deficits have been reported in
rat models (4,6,7,20,21) and in the early
stages of Parkinson’s disease, even before
the onset of motor symptoms (22). Since
MPTP- and 6-OHDA-lesioned rats model
the early and advanced phases of Parkinson’s
disease, respectively, the present results encourage
future studies to test whether the
observed neuroprotective effect of K/X
would delay neurodegeneration in both
phases of this disease.