الفهرس 
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Abstract
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SUMMARY AND CONCLUSIONS
Schizophrenia 1s a major psychotic disturbance of
non clear aetiology that results in severe and
’ prolonged mental disturbance.
The cause of schizophrenia may be due to genetic, and
environmental factors, or biochemical changes.
The drug treatment can eleminate or reduce symptoms of
schizophrenia. Neuroleptics drug therapy is the commonset
component used for treating schizophrenic disorders, but
there are many reports on the effective use of propranolol
in controlling schizophrenic symptoms, and neuroleptic
induced extrapyramidal manifestations.
The aim of the present work was to evaluate the
amphetamine model of induction of schizophrenia in rats, and
to study the neurotransmitter pattern namely norepinephrine,
GABA, dopamine and serotonin , as well as to suggest the
causative mechanism of the disease in this model. Moreover
the effect of a single dose of chlorpromazine, and
propranolol singly or 1n combination on tested
neurotransmitters in the whole brain and its areas (namely
cerebral cortex, Thalamus, hypothalamus, midbrain and
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hindbrain}. The experimental findings were assessed in terms
of their relevance to the therapeutic usefullness and side
effects.
Male albino rats of about 100-120 gm were chosen
1n this study. Animals were divided into 5 groups each
consists of 60 rats, the first group was several as a normal
control group, in the second group schizophrenia was induced
by a single S. C. injection of amphetamine (5 mg/kg B. W. },
the third, fourth, and fifth groups of amphetamine induced
schizophrenic rats served to study the effect of
chlorpromazine ( 12, mgjkg B. W.,s. C. ) , propranolol ( 30 mgjkg
B. W.,L P.), and combined drug respectively on norepinephrine,
GABA, dopamine, and Serotonin in the whole brain and its
different areas namely cerebral cortex,
thalamus-hypothalamus, midbrain and hindbrain. The choice of
the dose based on pilot experiment and published literature.
The method of Sourkes and Murphy, (1965) were adopted
for the determination of norepinephrine and dopamine,
while that of Weissbach, {1965) was used for serotonin
evaluation,and the concentration of GABA was assessed by
using the chromatographic method of Consden et al, {1944).
The findings in this study revealed that amphetamine
induced schizophrenic rats showed a significant increase of
norepinephrine, dOPamine, and serotonin concentrations, this
increase may be attributed to increasing release, of
monoamines and/or inhibiting of their reuptake,
to the monoamine oxidase inhibitory effect of
moreover the increased level of GABA may be due
in addition
amphetamine,
to its a
1
adrenoceptor stimulant effect of amphetamine. The results of
this work may indicate that the elevated synaptic
concentration of norepinephrine probably gives rise to
excitation, and that of dOPamine may be responsible for
locemotor hyperactivity, and while the r1se in synaptic
concentration of serotonin may explain alerteness, elevated
mood and depressed appetite in schizophrenic psychosis.
The rised GABA level may act as a compensatory mechanism to
reduce excitatony state of schizophrenia.
Administration of chlorpromazine
normalization of dopamine concentration
resulted
through
adrenoceptor blockade, as well as,significantly reduce
in
level of norepinephrine through presynaptic a adrenoceptor
2
blockade, in addition GABA concentration was increased
through blocking its reuptake.The above mentioned effect may
be contribute the antipsychotic effect of chlorpromazine.
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Tbe da~a of the present work may explain extrapyramidal
syndrome and gynaecomastia, induced by chlorpromazine, these
effects may be due to D
2
receptor blockade. The sedative
effect of the drug may be due to decreased norepinephrine
and eleveted GABA concentration in cerebral cortex.
The hypotensive effect of the drug may result from
increased levels of GABA and serotonin in thalamun and
hypothalamus, in addition to increased GABA and decrease
serotonin concentrations in hindbrain. the rise in serotonin
level in thalamus and hypothalamus may explain inhibition of
ovulation induced by chlorpromazine.
Propranolol exerted its antipsychotic effect by the
same mechanism as chlorpromazine {significantly decrease
norepinephrine, normalization of dopamine concentrations
through increasing release of these transmilters, increased
GABA level through B
1
adrenoceptor blockade) but
extrapyramidal symptoms that are common with chlorpromazine
do not occur with propranolol, this may be due to increased
level of serotonin.
Also from the data of the present work, we may conclude
that the sedative effect of propranolol may be due to
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decreased norepinephrine, increased GABA and
concentrations in cerebral cortex.
serotonin
The anithypertensive effect of propranolol may be due
to increased release of norepinephrine which then stimulate
a adrenergic receptors 1n hindbrain to lower systemic
2
arteral blood pressure.
The concomitant administration of propranolol and
chlorpromazine run in the same line and produce transmitter
pattern similar to that of propranolol but differs from
that of chlorpromazine in elevating serotonin level and this
may explain the low incidence of extrapyramidal symptoms
with the combined therapy.
A further study is needed to determine the local
concentration of each drug in brain and its areas, together
with determination of the receptor density in amphetamine
model of schizophrenia.
A further study is also needed to compare equipotent
doses of chlorpromazine and propranolol, and studying the
side effects of long use of combined drug therapy.