The dynamics of catecholamine content were studied in the adrenal glands and in various region of the brain of white rats under hypokinesia and injections of neurotropic agents. Profound changes in body catecholamine balance occured as a result of prolonged acute restriction of motor activity. Adrenalin retention increased and noradrenanalin retention decreased in the adrenal glands, hypothalamus, cerebral hemispheres, cerebellum and medulla oblongata. Observed alterations in catecholamine retention varied depending upon the type of neurotropic substance utilized. Mellipramine increased catecholamine retention in the tissues under observation while spasmolytin brought about an increase in adrenalin concentration in the adrenals and a decrease in the brain

Melnik, B. E.

Paladiy, E. S.

English

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THE CONTENT OF CATECHOLAMINES IN THE ADRENAL GLANDS
AND SECTIONS OF THE BRAIN UNDER HYPOKINESIA
AND INFECTION OF SOME NEUROTROPIC AGENTS
B. E. Melnik and E. S. Paladiy
(NASA—Tti- 76010) THE CONTENT OF
N8U -28044
CATECHOLAMINES IN THE ADRENAL GLANDS AND
SECTIONS OF THE BRAIN UNDER HYPOKINESIA AND, ^^ 	 Unclaa
INJECTION OF SOME NEUROTIiGPIC AGENTS 
1^^^	 63/52 28017(National Aeronautics and Space
Translation of "Soderzhaniye katekholaminov v nadpochechni ka
kh i otdelakh
gc:'lovnogo mozga pri gipokinezii i vvedenii nekotorykh neyrotropnkh
sredstv," Biologicheski ye nauki, Vol. 15, No. 11, 19722 pp. 45-W
^1t^, •^ rC^l	 0
RGCEIV'ED
4^ASA S^1 ^ACIl.1T't
l^CCCSS D'EpT. ..':
f 	 ^
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION
WASHINGTON, D.C. 20546	 MARCH 1980
STANDARD TITLE PAGE
1,	 i.cp .er "J ,	 2	 Govitmmont Aceessron Na.
	
Pn-
3,	 Reoipinnt ' s Catalog No,^
Report Date
March 19$0a. Title and Subtitle THE CONTENT OF C A4TSCHOLAMINEF3
5.
IN THE ADRENAL` GLANDS AND SECTIONS OF
6.	 Performing Organization C odeTHE BRAIN UNDER HYPOKINESIA AND I NJE CT-
TIQN.. ,	
-	
^IEiTII (^TRS2F' r.	 AGENTS
B. 
I":ar(Ael 1 
nik and E.	 S.	 Palad iy
Department of Human and Anima. Physiolog
V. I. Lenin Kishinev State University
8.	 Performing Organisation Report No.
1a.	 Wor{	 Unit No.
11.	 Contract at Grant No.
NASW- 1 9
—-- _------
9,	 Performing Organisation Name and Address
Leo Kanner Aosoc iates
Redwood City, California 94063
13.	 Type of Report and Period Covefed
Translation
12.^ Sponsoring Agency Name and Address
National Aeronautics and Space .Adminis-
tration, Washington, D.	 C.	 205116
14,	 Sponsoring Agency Code
15.	 Supplementary Notes
Translation of "Soderzhaniye katekholaminov v nadpochechnilcalt
i otdelakh golovnogo mozga pri gipokirtezii •i vvedenl.i nekotory
neyrotropnykh sredstv," Biologieheskiye nauk3, Vo... 15, No.	 11,
1 972, pp .	 45-49.
16,	 Abstract
White rats (75) were studied.	 Profound changes in body cate-
cholamine balance occurred as a result of prolonged acute
restriction of motor activity.
	 Adrenalin retention increased
and noradrenalin retention decreased in the adrenal glands,
hypothalamus, cerebral hemispheres, cerebellum and medulla
oblongata.
	 Observed alterations in catecholamine retention
cried depending upon the type of neurotropic substance util-
ized.
	 Mellipramine increased catecholamine retention in the
issues under observation, while spasmolytin brought about
an increase in adrenalin concentration in the adrenals and a
decrease in the brain.
17.	 Key Words (Solccted by Author(s)) 10,	 r;	 trtbution Statement
Unclassified-Unlimited
19,	 Security Clossil. (of this report) 20.	 Security Classif. (of this Pogo) 21• No, of Pages 22,	 Price
Unclassified Unclassified 10
NASA•N
:h
t-
i
i
THE* CONTENT OF CATEXHOLAMINE".3 IN THE' ADRENAL
GbANDS A14D IS)ECTIOMB OF THE IMAIN UNDER 11YPO-
KINESIA AWL) INJECTION OF SOME  DIEUROTROPIC AGENTS)
13. E. Nel l nik and E', 11. Paladiy
Department of Human and Animal Physiology
V. 1. 1,enin Kishinev state University
Kishinev, Us""R
In experiments on rats 1" was established that, tinder -the 	 /45*
influence of comparatively prolonged acute restriction of motor
,activity, profound alterations in the catecholamine balance occur,
manifested as an increase in the content of epinephrine and decrease
in the content of norepinephrino in the adrenals, hypothalamus, -
cerebral hemispheres, cerebellum, and medulla oblongr ata. It was
shown that the observed alterations in catecholamine oontent may
be compensated through the use 
of 
corresponding neurotropic substance,-,.
Mellipramine facilitates an increase in the content of catecholamines
in the tissues tinder study, while spasmolytin causes vn increase in
the concentration of crinophri,io in the adrenals and a decrease in
the brain.
The harmful effects of decreased motor activity (hypokinesia)
on the condition of human and animal body physiological functions
have recent],y become of increasing interest to biologists and
physicians. It has been established that restriction of motor activity
invariably leads to disorders in a number of metabolic processes
and physiological systems which function as regulators, for example,
those producing hormones and mediators, in ),,.articular catecholamines
E 2 1 ,14 1 5, 7 p 8 1,
Cateoholamines are present in various functional and struct-
ural regions of the brain and adrenals, and play an important role
in the mechanisms of nhysiological processes. In this connection,
the search for substances which normalize disordered catecholamine
dtotabolism in the body and ways of using neurotropic pharmacological
, a
1
substances is assuming great practical significahoo.
tare studied the dynamics of catecholamine content in the adrentals
and in various regions of , the brain Curing acute restriction of body
motor activity.
Experiments were conducted on white laboratory rats of both
sexes, 75 animals were used, havin g
 pro-experiment weights of
160-200
In experiments of the first series, the change in catecholamine
content in the organs under study was exomined followinS 7, 14, and
21 days of acute motor activity restriction. In experiments of the
second series, the same indices were studied following 7 and 14 days
of motor activity restriction, with daily injection of neurotropic
substances into the experimental animals. One of the animal groups
received injections of mellipramine, 6mg, per 1kj T,. body weight, and
the other received spasmolytin, 4mg /kg over the course of the entire
experiment. Intact rats kept under normal vivarium conditions without /46
restricting activity served as the control.
In order to create hypokinesia, the animals were placed in special
panelled cages, set up according to the shape and size of tho animal,
The construction of the cages permitted systematic removal of food
wastes, urine, and fecal substances, and supplied water and feed
to the animals. The animals received unlimited quantities of water
and food.	 The cages and animals were kept at a relatively constant
temPerature and received moderate natural illumination. Before
placing the rats in the cages, theywere weighed and their temperntures
taken. Over the course of the entire experiment, body weights of
the experimental and control rats were taken and rectal temper-
ature was recorded daily. The results of the measurements were
worked up using variation statistics and Student's method.
At .-a preselected time,,the rats were decapitated and "L.,he content
of catecholamines (epinephrine and norepinephrine) in the organs and
tissues was determined. 	 Epinephrine and norepinephrine content in
2
Fr-	 1 77
the adrenals and various regions of the brain (hypothalamus, cerebral
hemispheres, cerebellum, and medulla oblongata) was determined
using V, 0. Osinskqya l s fluorometric method [6]. Fluorescent
intensity was measured using a PF-1 domestic brand fluorometer,
using excitation waves of 360 nanometers, obtained from a URW
primary light filter. Yaximum fluorescence corresponded to a
frequency of 510 nanometers, obtained through a secorlary inter-
ference light filter.
Analysis of the statistical data indicates that hypokinesia
over the course of the entire experiment caused a trustworthy
progressive increase In epinephrine content in the adrenals
(Table 1). Nhus, following seven days of hypokinesia, epineph-
rine content in the adrenals increased almost two times, while
following 21 days it increased almost five times relative to the
controls.
Change in norepinephrine content in the adrenals occurred
in two phases: a decrease took place on the 7th day of the exper-
iment, while on the 14th day there was a maximum increase in the
quantity of this substance in the adrenals. The decrease in
norepinephrino concentration in the adrenals, apparently, was a
consequence of elevated output of it into the blood, and was prob-
ably associated with the passive anxiety of the animals.
Acute restriction of motor activity caused considerable fluc-
tuations in the concentration of catecholamines in the brain tissues
under study, which undoubtedly is evidence of alteration in the
mechanismv of nervous processes. By the 7th day of the experiment,
epinephrine content in the hypothalamus increased almost 5 times
relative to controls, and in the corebrvl hemispheres increased 3
times. A noticeable increase in the quantity of epinephrine was
also established in the cerebellum and medulla oblongata following
7 days of acute hypokinesia. Further increase in epinephrine content
in both the hypothalamus and cerebral hemispheres occurred by the
14th day of the experiment. 	 In the cerebellum and medulla oblongata,
Ithe quantity of epinephrine did not chani e, or perhapo decreased
somewhat, in comparison to the 7th day of tite experiment; by the
21st day, a Curther moderate increase in epinephrine content was
F	 noted in the hypothalamus, cerebellum, and medulla oblonc,ata
(Table 1) .
Acute restriction of the animals' motor activity caused an
increase in the concentration of norepinephrine in all the regions
of the brain under study: in the medulla. oblongata - over the
course of the entire experiment, in the hypothalamus, cerebellum,
and cerebral hemispheres - by the 14th and 21st days of the
experiment.
The considerable alteration in the distribution of catechol
amines in various regions of the brain during hypokinesia must be
examined within the framework of autoregulatory neurohumeral proc-
esses, The high content of epinephrine an, products of its
oxidation were evidence of intensification of metabolic processes,
which may lead to tissue hypoxia. Moreover, the large quantity of
catecholamines changes the energy balance, which is harmful to the
overoll functional condition of the body.. In particular, energy
balance disorders manifest themselves in processes associated with
acetylcholine synthesis, and may have an effect on the functional
condition of the nervous system as a whole.
Results of experiments using injection of neurotropic sub,_ 	 247
stances into immobilized animals are of considerable interest
(Table 2).	 In the first stage of the experiment, the neurotropic
preparation mellipramine caused a distinct increase in epinephrine
and norepinephrine content in the animal tissues under study, in
comparison to the tissues of animals which were kept immobilized
but did not receive mellipamine. Epinephrine concentration in
brain tissues began to gradually decrease on the 14th day.	 a
Norepinephrine content in brain t,issucs grew sharply in the
1st half of the experiment, and on the 14th day it continued to be 	
1
l
4
	 a
higher than in animals subjected only to immobilization. Upon the
injection of mellipramine, norepinephrine content decreased so
abruptly that we could not detect it. This fact may be evidence
of sympatico-adrenal system function exhaustion, ,which is an
unfavourable symptom and must be taken into account when Makinr,
an overall evaluation of the reactivity of the body to prolonged
hypokinesia, It has been suggested [4] that mellipramine, as an
antidepressant, has an effect at least on P regions of the brain:
the hypothalrimufi, in its posterolateral regions, and the amy,r*,-
daloid complex,'in its basiolateral part.
Injection of the immobJ 1. j z-&d 6.^n l4aals with spasmolytin caused
a two phased change in epinephrine content in the adrenals: a
considerable increase was noted following 7 days, and a sharp
decrease of epinephrine content in the adrenrals relative to
controls (immobilized animals), was noted following 14 days,
Injection of spasmolytin and immobilization over the entire
course of the experiment caused a moderate decrease in epincbphrine
content in the brain tissues under study. Following injection
	 /49
of sposmolytin, norepinephrine quantity in the adrenals of the
immobilized rats decreased sharply following seven days and
continued to decrease for 14 days of the experiment. Morepinephrine
content increased in the brain tissues, with the exception of^;;',..
the cerebellum.
The effect o.,
 spasmolytin on the indices we studied may be
explained by blocking of the cholinergic system of 'the cerebral
cortex and hippocampus, since we know that expanded cortical,
inhibition causes an increase in the content of norepinephrine in
brain tissueEll .
The results of the second series of experiments indicated that
alterations in catecholamine content observed in various tissues
during immobilization may be successfully modified through injection
of the corresponding neurotropic substances.
" I
5
All of the above leads uo to conclude that protracted liypokinesia
cautc,es profound chraigoo in catecliolnmine mietabbliom in animal.s, which
is manifested by an increase in epinephrine content and decrense in
norjpinoptirine quantity in all ti,srjues under study, The nervous
,ystetit stimulator nellipramine causes an increase in vatecholamine
content for the tiosues under study in such anit,lalo. Tile N-cholin-
olytic opasmolytin, increases epinopYirine content in the adrenals
during hypokinesia, and decreases its quantity in brain tissues.
4.24:0,45 2.1.11'0.45
I'<0.1 I)<0' 05
1.25:!:0,18 2.1tO,86
P<0,02 P	 0.l
2,2!-0,93 1.86±0,19
I)<0I I 1)<O.()01
3,5-!'0,02
1.41+0,&1
P .10,rxr2
I , 01±11, 77
2,0.9:!'0.&12,7; •x•0.57 4,42*0,(1
P< 0.05 1 P<0,02	 Px •(1, (x)2
1.70±0,r'..9 1.21-1-0,11 2,08±0,24
p ±,6.",1- (1.46 3,86•-1,77
I1<o, I P	 O,(r2
7,16±0,91 0,I,,t0.(X)5 ;{	 ,19 4:I,r le
1)<O,on1 I'•;(l,02
 1'	 16,15
TABLE 1. CHANGE IN CATECHOLADIINE CONTENT IN THE ORGANS OF RATS
FOLLOWING ACUTE RESTRICTION OF MOTOR ACTIVITY
w0
Cond r ns k M Catecholamine content, micro gra s	 er lg.i raw tissue nedullaof	 ,^ adrenals hypothalamus cer	 *ar11ema. pl eres cerebellum O l ongata
I xprmnt	
^
A N	 A N A N A N A	 N
1316 •#76 • ^r31.3	 1,940 ,32 3,T3,*_O. kl .3e9^0,121i ( ► ,512,	 0,142 0.5250,09' 1,01:0,012 0,148$ 0, ,282	 0151:to. ^J3ont..^ryol ..	 G
1 11mmWh	 9 3.24'±0, ri7 0.49 2,24-0 .33 0.54±°0.(MJ5 ' N	 0, 191.	 4;0.270,92°±
4 days
2315!•98
1)<0,001 282±00,77 6,24a0,90I)	 0r l	 P<.O,001 2,0°0.751 1<0.05 1)$„0,001
:MOM
P t ll,1 1' ^ Cr.O(11 P< ,0.001 I '<011	 11<0.05
mmobil r n	 I( 3103 •±x 198 460:1:34.5	 7.27•±0.58 1.62:tO.37 4,0'9'±'0.!11 (1, 841:,+:0.1 2,17±0.27 1,21;tOo15 1,08±'0,2
21 days 11<0.001 11<0.012I)<0.001 ,1;0,001 1 0<01(411 1 1"'0.1 P<0.(X)I 1 ►^^0,1 I	 1 ►^,u.u:
Immobil I n 9 5220°t4111 1.;1:-2'9,2710.7.1; 0,95 5,15.:0.51 1,01 •!•(1.3 1.)91±0.28 2.2210.31 1.7$'±• 0,19 I.CrI!°r1,2ri	 if	 w:t1l.-II
I'R ;0,1X11 1'<0.1	 It'0,001 P<^0,01 P<•().(X)l R<I),(X)1 1)x.0,001 1 15,0.(X11 I'«,O, I	 It.°.,0,1'2
Key: A -- adrenaline
N -- noradrenaline
TABLE 2. CATECHOLAMINE CONTENT IN THE ORGANS OF RATS FOLLOWING
ACUTE RESTRICTION OF MOTOR ACTIVITY AND INJECTION OF
NEUROTROPIC SUBSTANCES
44
0
Condrns
of	 ra
hxprmnt
7 days
Immobil In 5
19mgBYT rn
7days Imm.
+melliprmn a
14 days
ImmobilIn
+melliprmn a
7 days
+spasmoltn a
14 days
Immobilrn
+spasmoltn 8
2274±,95,57 270±22,8
29)J2±150,6 470.55,5
320r1±385 0
PLO, 05
2723:!:424,4 0
P^ O,1
7376±592 0
P<0,001
106,±12,0 22u_90,7
P<0,001 P<O, I
3,3:0,42 51183:0,41 1.16±0,3
P-,0,01 I P<0,1	 I I' -'0,01
1,5 •±'0.29 1 1,25°±0.29
P<;O,(1( ► 1	 P^'CI,(15
6,90:0,512 1,75±0.2
11.25:E2,P 20,0-!•2,88
P<0,05 P <0,01
1,66 :!•0,41 120±2.01
P,<n,001 P<0,05
2.04±0,41 4.58•!'0.41
P`0,0a,. P.--0,01
Catecholamine content, micrograms per lg. raw tissue
adrenals	 hypothalamus' ereb al
	 cerebellumhemispheres
A	 N	 A	 N	 A	 N	 A	 N
2,48: 0.4811 0,45 .00.0771 2rH!'n. irn l 0.5'! 0. III
4,02±0,71 0,871:!•0,012 
	
1.28±0.15
,
ooionbata
A	 I N
1.1:1±0,183 0,8'J=:O,10
1,124.0,153 1,31:0,111
Key: A - adrenaline
B -- noradrenaline
I
7
REFERENCES
.. Andreyev, S. V., and 1. A. Kobkova, in: Rol l katekholaminov v
,,dorovom i bol l nom organizme [The Role 	 ateclio a roes ^n the
Healthy and Diseased Body'j, "Medicine" Publishing house, Moscow,
1970.
2. Artyukhina, T. V., "The Structural Condition of the Hypothalamo-
hypophyseal System during Hypokinesia", in: Eks2orimental l pyy ee
issledovaniya ipokinezii, izmenennoy gazovoy :redy, uskoreniy,
pereE;ruzok i drugikh faktorov LExperimental Studies on Hypokinesia,
Altered Gaseous Environments, Acceleration, 2-forces ) and Other
Factors], Moscow, 1968.
3. Korobkov, A. V., L. A. Toffe, M. A. Abrikosova, Yu. M. Stoyda,
"The Dynamics of OrthostatIc Stability in Athletes as Affected
by 40--day Hypokinesia", Kosmicheskaya biologiya i meditsina,
2, 3 (1968)•
4. Lapin, 1. G., and L. Kh. Allikmete, "A Hypothesis Concerning the
Role of the Amygda,loid Complex and Hypothalamus in the Action
of Antidepressants", in: Sovremennyve psikhotropnyye sredstva
[Contemporary PsychtropicRemediesj, 2nd Edition, Moscow, 1967.
Mel Inik, B. E., and F. S. Paladiy, "Alterations of Catecholamine
Content in Various Regions of the Brain and in the Adrenals
during Acute Hypokinesia", Materialy nauchnoy konferentsii
,Materials from the scientifi c Converence of the Kishinev btave
University Faculty Summarizing; Research Work in 19691, Kishinev,
1970.
6. Osinskaya, V. 0., "Research on Epinephrine and Norepinephrine
Metabolism in the Tissues of the Animal Body", Biokhimiya,
22, 3 (1957)
7. Parin, V. V., V. N. Vinogradov, A. N. Razumov, "Problems in
Space Pharmacology", Kosmicheskaya biologiya i medits_ina,
1 (1969).
8. Parin, V. V., B. M. Fedorov, V. S. Nevstruyeva, "Alterations in
Corticosteroid and Catecholamine Metabolism during Acute
Restriction of Body Motor Activity", Dokl. AN SSSR, 184, 1 (1969).


The content of catecholamines in the adrenal glands and sections of the brain under hypokinesia and injection of some neurotropic agents

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