الفهرس 
Material and methodsOnly 14 pages are availabe for public view
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Abstract
The introduction of beta-adrenergic blockers in
clinical medicine was recognized as one of the major
therapeutic advances of this century. Beta-adrenergic
blockers which have been used for many years in general
medicine are still being explored for new indications. One
of such areas is the effect of beta-blockers on the central
nervous system.
There are many reports on the effective use of
propranolol in controlling neuroleptic-induced
extrapyramidal manifestations. Akathisia for example is a
frequent and often disabling side effect of treatment with
neuroleptic drugs. The traditional treatment of
neuroleptic-induced akathisia has been disappointing.
Beta-blockers especially the non-selective members may
induce hypoglycemia particularly in diabetics under therapy
due to impairement of the normal sympathetic-mediated
homeostatic mechanisms for maintaining the blood sugar. The
symptoms of hypoglycemia as mediated by the sympathetic
system will not occur. Such a prolonged-non detected
Summary and Conclusion 151
decrease in brain fuel may be expected to affect brain
functions such as learning and memory.
The aim of the present work was to study the effects
of beta-blockers (either non selective as propranolol or
selective as metoprolol) on two important aspects of brain
functions namely motor behavior and learning process. This
works consists of two parts :
Part r : This part concerned with the study of the effect
of propranolol and metoprolol versus benztropine on
motor behavior.
An animal model of Parkinsonism was made by a single
s.c. injection of fluphenazine in rats (10 mg/kg B.W.).
Propranolol (in doses of 5, 10, 20 & 40 mg/kg), metoprolol
(in doses of 7.5, 15, 30 & 60 mg/kg) or benztropine (1
mg/kg) were injected s.c. for 15 days either concomitantly
(as prophylaxis) with/or on the third day following
fluphenazine injection (as treatment). Motor coordination
was determined using the Rotord test (Hoore and Rech,
19”), as the time in seconds that the rat can keep its
posture on a rolling bar. After 15 days all animals are
sacrified and their brains were extracted and dissected,
whole brain, thalamus and hypothalamus contents of
Summary and Conclusion 152
acetylcholine and dopamine were estimated biologically
according to Richter and crossland (1949) for acetylcholine
and with the flurometric method of Bourke and Murphy (1965)
for dopamine.
We found that benztropine (1 mg/kg) and propranolol
(40 mg/Kg) medicated groups were non-significant from the
control non-medicated group from the 1st day indicating a
prophylactic effect. other doses of propranolol produced
the effect in later days. Metoprolol on the other hand
failed to produce this effect in all doses used but still
significant from the fluphenazine group.
Regarding brain transmitters, both benztropine (1
mg/kg) and propranolol (40 mg/kg) could increase dopamine
level to reach that of the non-medicated control group.
Metorpolol (60 mg/kg) could not produce this effect.
Regarding Ach, only benztropine offered levels nonsignificant
from the non-medicated control group, while
propranolol and metorpolol could not produce this effect.
Benz tropine (1 mg/kg) and propranolol (40 mg/kg)
could produce a curative effect from the 1st day.
Propranolol (10 & 20 mg/kg) produced this effects after few
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Summary and Conclusion 153
days while propranolol (5 mg/kg) and metoprolol in all used
doses had no curative effect.
The -corresponding brain neurotransmitters are also
estimated. Regarding dopamine, both benztropine (1 mg/kg)
and propranolol (40 mg/kg) could increase its levels to
those of non-medicated controls while metoprolol failed to
produce this effect. Regarding acetylcholine only
benz tropine could reduce its level to be non-significant
with those of non-medicated control group.
Part II : to study the effect of propranolol and metoprolol
on the learning process using the learned conditioned
reflex according to the same rules described by Grant
(1964) in normal and insulin-induced hypoglycemic rats
in order to investigate the implication of
hypoglycemia in the process of B-blockers induced
amnesia.
Animals were administered a daily S.C. injections of
insulin (2.5 and 5 I.U/kg) and/or beta-blockers
(propranolol in doses of 10, 20 & 40 mg/kg or metoprolol in
doses of 15, 30 & 60 mg/kg). Animals were tested for the
learned conditioned reflex 5 times a day for each animal.
After conditioning reinforcement was given by 3 days trials
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summary and Conclusion 154
till the time of experiment for extinction. The latency
period in days till the animal learned the reflex as well
as the number of positive trials needed to get rid of the
reflex (extinction) were recorded.
Serum glucose level was estimated utilizing the
methods of Trinder (1969), before drug administration and
after testing of each animal.
We found that propranolol (10 mg/kg), metoprolol (15
mg/kg), insulin (2.5 1.U/kg), insulin + propranolol or
metoprolol (same doses) failed to produce any significant
effect on latency period of rats to acquire the conditioned
reflex. On the other hand in all these groups, except the
group received metoprolol alone, extinction was
significantly reduced. The corresponding serum glucose
level showed a significant reduction in all groups allover
the experiment except with those administered propranolol
or metoprolol.
with high doses (5 I.U/Kg insulin, 20 mg/kg
propranolol and 30 mg/kg metoprolol, the group receiving
insulin and propranolol together increased significantly
the latency period for rats to develop the reflex while
other results was about the same with smaller doses. The
corresponding serum glucose level still shows a significant
summary and Ccnclusion 155
reduction among all grcups receiving insulin but not with
those administered propranolol or metoprolol alone.
with more higher doses of propranolol (40 mg/kg) and
metoprolol (60 mq/kg) and the same dose of insulin (5
I.U/kg), the group receiving insulin and metoprolol
together could significantly prolong latency period and the
group administered metoprolol alone could significantly
prolong extinction while other results were similar to
those with smaller doses. The corresponding serum glucose
level still shows a significant reduction among all groups
administered insulin but not in the groups of B-blockers
alone.
So it can be said that propranolol may be used as
curative and prophylactic against antipsychotic inducedextrapyramidal
manifestations as alternative to the usually
used anticholinergic drugs especially in cardiac patients
and in cases where anticholinergic proved contra-indicated
or uneffective. Also, we can conclude that B2 adrenoceptors
are important in the process of learning, and hypoglycemia
shares in part in disturbing this process. So when insulin
and B-blockers are to be given in combination, a
cardioselective B-blocker is preferred to avoid the
implication of B1-blockade on learning and memory.