Objectives : Phencyclidine(PCP) or PCP-like substances such as ketamine have been
know to rekindle the cognitive dysfunction in schizophrenia. The aims of this study
were to identify whether PCP-like substances can produce cognitive deficit in
schizophrenia, to discuss relation with aging process, and finally to speculate underlying
neurochemical mecha-nisms by various drug responses.
Methods : In experiment I, radial maze tests were done in 24 Sprague-Dawley rats
for 3 days to get baseline data. Being divided into 4 groups(6 rats respectively) of
normal aged, normal adult controls, atropine-treated and ketamine-treated, the radial
maze tests were repeated on every week for 6 weeks, and then the rats were sacrificed
by intracardiac perfusion with phosphate-buffered 10% formaldehyde solution for
histology. The brain specimen was stained with hematoxylin-eosin to count cells in the
prefrontal cortex and hippocampus. In experiment Ⅱ, radial maze tests were done for 48
rats before any drug treatment and only after ketamine administration. Thereafter,
haloperidol, bromocriptine, clonidine, nimodipine, tacrine, valproic acid, naloxone and
fluoxetine were intramuscularly injected on every other day in addition to ketamine.
Radial maze tests were repeated on every week for 6 weeks, and then rats were
prepared by the same procedure for histology.
Results : 1) Reaction times of radial maze tests of atropine-treated rats were
significantly prolonged than those of normal aged(p<0.05) or normal adult
controls(p<0.05). Cell numbers of prefrontal cortex & hippocampus in ketamine-treated
rats were significantly reduced than those in normal aged(p<0.05) or normal adult
controls(p<0.005).
2) Reduced cell numbers by ketamine became significantly raised by tacrine
administration in prefrontal cortex $ hippocampus(p<0.05), while there were no
significant changes on radial maze test. Cell numbers also tended to be raised by
nimodipine, fluoxetine and haloperidol administration.
Conclusions : In conclusion, the visuospatial memory disorders in ketamine-induced
psychotic rats might be partly associated with aging process. Furthermore, the responses
to the various drugs suggested cholinergic system might have an important role in the
neurochemical mechanism of the cognitive dysfunction in ketamine-induced psychosis.
Otherwise, calcium metabolism as well as serotonergic and dopaminergic systems
seemed to be possibly related.
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