Effect of Clonidine on Acetylcholine Content of Rat Brain

Ap'i:-June
1981
I~d. J. Phvsiol, Pharrnac.
Iral nervous system
by
theo-
ffe.t of caffeine versus placebo
967.
ted by Wllliams
RH.
Philad=t-
LETTERTO THE EDITOR
phOsphorylasein skeletal muscle
EFFECT OF CLONIDINE
ON ACETYLCHOLINE
CONTENT
OF RAT BRAIN
snon on oral glucose tOlerance
Ihomimetic amines.
o stressIn man.
Arch. Int,
(Received
Nature. 210 :
on July
25. 1980)
7: 1042-1046,1968.
ary hormones,
Endocrinology,
Sil.
n. London : Oxford University
10caffeine and coffee.
Mete-
I calecholamines in rats during
lucagon-induced and rotbuta19-820, 1967.
an between plasma free fatty
0, 1971.
"Hunger: basic mechanisms
York, Raven Press, pp. 1 -18.
adrenergic mechanisms in th"
ancreatic islets of rat in vitro.
glucose level.
Clin. Endocr.
il/ey & Sons, pp. 166-168.
, - cyclic monophosphate
. 834-836. 1972.
and
e from the adrenal medulla.
cadernic Press, 1971.
"Endocrinology". edited by
einberqer and AI. Winegard.
following cigarette smoking
242, 1980.
•
s and glycogenolysis
In VIVO.
." edited by Williams.
R.H.
A stimulation of central presynaptic ex-2 adrenoceptors seems to be involved in antihypertensive effects of clonidine. as well as in sedation. it consistantly produces in man and
in animals (5).
Since many sedatives and other depressants are known to alter the brain
acetylcholine (ACh) levels (1. 2. 4) it was of interest to study the effect of clonidine on
brain ACh content of rats.
Young albino rats (120-190 g) were divided in 4 groups (6 animals per group).
One group was injected with clonidine hydrochloride (100 ",g/kg. ip); another group
received equivalent volume of normal saline only.
The third group also received clonidine
but was given phenoxybenzamine
hydrochloride
(10 mg/kg. ip) 1 hr before clonidine
Injection. The fourth group received phenoxybenzamine
hydrochloride (10 mg/kg.
ip)
alone.
The animals
were decapitated
1 hr after various
treatments.
The brains were
excised. weighed and homoginized in ice-cold normal saline containing physostigmine
sulphate (15 ",g/ml) and cupric chloride (17 Jl.g/ml).
Free and bound ACh was extracted
by the method of Crossland (2).
The ACh content of the extract was estimated (within
24 hrs) using the frog rectus abdominis muscle sensitized with physostigmine (1 ",g/ml
of bath fluid), by four-point assay method.
The ACh content was expressed as ",g/g of
fresh tissue (Ta ble I).
It will be seen that treatment with clonidine caused 27.6% and 42.4% decrease in
total and free ACh content of rat brain respectively.
This decrease caused by clonidine
was significantly antagonized by phenoxybenzamine.
Phenoxybenzamine alone did not
caUS3 any significant
change in ACh content of rat brain.
190
Letter to the Editor
April-June 1981
lnd. J. Physiol. Pharrnac,
TABLE I:
Effect of clonidine on the acetylcholine content of rat brain and
its antagonism by phenoxybenzamine.
n=
Treatment
Normal saline, ip (control)
Clonidine HCI (100 pg/kg,
i p)
Phenoxybenzamine HCI (10 mg/kg,
as in (2) after 1 h
Phenoxybenzamine HCI (10 mg/kg,
-------
i p) +ctonidine
content
Free
LETTER TO EDITO
Mean±S.E.M.
Total
(v-g/g)
6
0.59±0.183
2.75±1.16
6
0.34±0.143*
2.0 ±0.202*
6
0.6
2.88±1.175*
6
i p)
ACH
±0.24*
0.58±0.616
VA
Sir.
Isoprenaline
response to this dr
13-adrenoceptor med
small doses, which
vasopressor activity
guanethidine
and c
2.71±1.18
------
n = number of animals.
*
The value differs significantly (P<O
05, t test) from that of the appropriate control group.
Evidence obtained using blockers of ex -2 adrenoceptors (3) shows that sedation
due to clonidine involves central presynaptic ex -2 adrenoceptors.
We have now found
that in rats a sedative dose of clonidine also decreases the brain ACh content. Our evidence
obtained with phenoxybenzamine
indicates that like sedation the change in brain ACh
content following clonidine is also mediated through the central ex -2 adrenoceptors.
S. Phadke.** R.K. Gupta and S.L. Agrawal
Department of Pharmacology,
Medical College, Jabalpur (M.P.)
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Present address: Department of Pharmacology. S.S. Medical College. Rewa (M.P.}
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2·
Mongrel dog
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Cyprohepta
17.7±7.20
(n=3)
and resistant to pr
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duced a biphasic e
tained ~ise. Vaso
(n=3).
In doqs tre
was hardly altered;
of either quanethic
appearance of any
drugs were adrnini
dependent vasopre
Fig.
Subsequen
1-B) or in bet
•
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