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Effects of panax ginseng root on acquisition of sound discrimination behaviour in rats
EFFECTS
OF PANAX
OF SOUND
GINSENG
ROOT ON ACQUISITION
DISCRIMINATION
Hiroshi
SAITO,
Moriyoshi
BEHAVIOUR
TSUCHIYA,
IN RATS
Shinichi
NAKA
and Keijiro TAKAGI* Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan * Department of Pharmacotherapeutics , Faculty of Pharmaceutical Sciences, Tokyo Science University, Shinjuku-ku, Tokyo 162, Japan Accepted
October
23,
1978
Abstract-Pole-climbing and shuttle-avoidance tests were employed to study the acquisition of conditioned avoidance response (CAR) and discrimination behaviour (DB) in male Wistar rats which had been given extracts from Panax Ginseng root intraperitoneally or orally. Neither a lipid soluble fraction (GNo. 5) nor a ginsenoside Rg fraction (GRg) produced significant changes in the acquisition of CAR. GRg given intraperitoneally produced a significant acceleration in the acquisition of DB between a 500 Hz signal sound followed by an electric shock (SD) and a 1000 Hz signal sound without a shock (SJ) in rats which had learned to avoid the shock following S1 at a rate of over 95 %. Small doses of GNo. 5 produced a significant depression in the acquisition of DB.
Several authors
(1-3)
have reported
activity of Panax ginseng root. for fractions
(GNo.
component
fatigued
of ginsenoside
activity.
were compared
neuropharmacological cological
properties
the response avoidance situation
5), from the results
with those of known
was then attempted.
The purpose
the pole-climbing
This may be an indication
of
of both fractions
of their
possible
pharma
a slight shortening
of
and shuttle
of sound stimuli in the avoidance the possible influence of
of CAR and of sound discrimination
and shuttle-avoidance
by blind
but drugs showing similar
(CS) in the pole-climbing
of the present study was to investigate
5 on acquisition
Rgl, the the
activity
the recovery
GRg and GNo. 5 produced
the discrimination
Rg) and lipid
Ginsenoside
from
Interpretation
stimulus
stimulating
is also assumed
(ginsenoside (4).
CNS-stimulants,
were not found.
tests, and GNo. 5 disrupted (6).
(5).
(CNS)
substances
accelerated
to 4 hr oscillation
latency (RL) to the conditioned
GRg and GNo.
(GRg),
Data on the CNS-stimulating
spectra
system
fraction
of blind screening
Rg fraction
states in the mice exposed
CNS-stimulating screening
nervous
of Panax ginseng root, such as the saponin
soluble fraction main
the central
The existence of CNS-stimulating
behaviour
(1313) in
situations.
MATERIALS AND METHODS 1) Pole-Climbing Test The experimental details of the apparatus and the procedure of training were as reported in our previous report (6).
Experiment 1:
Sounds of 500 Hz, which occurred intermittently once a sec and were 0.5
sec in duration, were delivered for 20 sec as CS; the stimulus consisted of sounds only for the first 10 sec and then sounds followed by electric shocks (unconditioned stimulus, 0.1 mA, 35 V, AC) for the remaining 10 sec. This training situation was repeated 10 times during an interval of 2 min per session.
Groups of 10 male Wistar rats (6-7 weeks old) weighing
150-170 g were given each drug and their training carried out in 2 sessions per day at 20 and 100 min after the injection for a week. Experiment 2:
Trained rats which were able to avoid shock stimuli of 500 Hz sounds (CS)
at the rate of over 95 %, were trained to discriminate between sounds of 500 Hz (SD) which were followed by electric shocks and those of 1000 Hz (S°) which were not followed by electric shocks.
The animals were exposed to both SD and S° alternately at intervals of
2 min for 40 min a day, at the same time day for 3 consecutive days.
This procedure was
started from 5 min after the injection of the drugs. Experiment 3:
Trained rats as in experiment 2, were exposed to 5 trials of SD and those
of S° by turns for 40 min a day, at the same time of day for 7 consecutive days.
This pro
cedure was started from 5 min after the injection of drugs. 2)
Shuttle-Avoidance Test The experimental details of the apparatus and the procedure of the training were as
described in the previous paper (7). Experiment 4:
Experiment 4 was designed the same as experiment 1 except for the test
apparatus and the interval of training (1 min). Experiment 5:
Rats in groups of 8 were used.
Naive rats were trained to discriminate between the sounds of 500 Hz (SD)
and those of 1000 Hz (S').
They were exposed to 10 trials of S° at an interval of 1 min,
and then for 5 min without either stimulus.
Ten trials of SD were then delivered at intervals
of 1 min, and after a following 5 min period of no stimulus, trials of S° were started again. The rats were exposed to this situation for 1 hr a day, at the same time of day for 3 consecutive days, 20 min after the administration of drugs. Experiment 6:
Trained rats (7) which had attained a 95-100 % performance level of the
CAR, were exposed to SD and S° alternately an intervals of 1 min for 40 min a day, at the same time of day, for 3 consecutive days.
This procedure was started at 30 min after the
administration. 3)
Rotating rod and Suspension Tests The rotating rod and suspension tests were performed to confirm the dose of drugs
which produced motor incoordination
and/or
muscle relaxation.
The rats were tested
4 times: 10, 40, 70 and 100 min after the i.p. administration, at the same time of day for 7 consecutive days, and 3 times: 40, 70 and 100 min after the p.o. administration for 12 days. 4)
Drug Tested GRg and GNo. 5 from Panax ginseng root were used.
A detailed fractionation
these compounds has been described in our previous report (6).
of
GNo. 5 was separated
into alkaline-soluble (GNo. 5-1) and -insoluble (GNo. 5-2) fractions.
GNo. 5, GNo. 5-1
and GNo. 5-2 were suspended in physiological saline with tween 80. The solution of GRg
was prepared with physiological saline.
Methamphetamine
eserine sulfate (ES) were used as controls.
Drugs were given once a day at the same time
of day, each day preceding the test.
hydrochloride
(MA) and
GRg, GNo. 5, GNo. 5-1 and GNo. 5-2 in doses of
10 and 30 mg/kg were given i.p. in the pole-climbing test. test they were given p.o. from 5 days before the test.
But in the shuttle-avoidance
MA in doses of 0.5 and 1 mg/kg and
ES in doses of 0.03 and 0.1 mg/kg were given i.p. in both tests.
Student's t-test was used
in every experiment for statistical assessment. RESULTS Experiment 1:
No fractions or drugs produced significant changes as compared with the
control in the acquisition of CAR.
GRg in doses of 10 and 30 mg/kg, MA 1 mg/kg and
ES 0.1 mg/kg produced a slight acceleration of the acquisition of CAR in the second session of the first experimental day and in the first or second session of the second experimental day, but this was not statistically significant. Experiment 2:
In the case of 10 mg/kg of GRg, the number of trials in which a rat did not
climb to S° was significantly larger than that in the control on the second experimental day (Fig. 1), but the climbing response to SD was not affected. GRg, 30 mg/kg also produced a similar effect, but it was not statistically significant. MA, 1 mg/kg produced a significant increase in the climbing due to S°. GNo. 5 and ES had no effect on DB to either SD or S°, though GNo. 5 in doses of 10 and 30 mg/kg produced a slight but not significant increase in S' climbing. Experiment 3:
The effects of GRg, GNo. 5, GNo. 5-1, GNo. 5-2, MA and ES on the
acquisition of DB in trained rats were observed repeatedly using a different procedure from that in experiment 2.
In the test using 10 mg/kg of GNo. 5 and GNo. 5-1, the number of
climbings up the pole by S° increased significantly in the 3rd and 4th days (Fig. 2).
No
FIG. 1. Effect of GRg and MA on acquisi tion of DB in the pole-climbing test. a) Percentage of trials of group in which rats did not climb in response to Sa. **: Symbols indicate the significant difference of group between the control and the drug-tested groups (p<0.01, Student's t-test) and * : (p<0.05).
FIG. 2.
Effect of GNo.
5, GNo. 5-1 and MA
on acquisition of DB in the pole-climbing test. See Fig. 1 for expression.
FIG.
3. in test.
Effect naive
of
MA
rats
in
See Fig.
on acquisition the
I for
of
FIG. 4.
DB
shuttle-avoidance
Effect
quisition learned
expression.
ing
sounds
avoidance
of
GNo.
5 and
MA
on
ac
of DB in rats which had to avoid electric shock follow of test.
500
Hz
See Fig.
in
the
shuttle
1 for expression.
difference in the number of trials in which the rat did not climb by SD was observed between the control and the GNo. 5 or GNo. 5-1 treated groups.
One mg/kg of MA also produced
a significant increase in the climbing in response to S° on each experimental day.
GNo.
5-2, GRg and ES had no effect on DB with either SD or S°, though GRg in a dose of 10 mg/kg and ES 0.1 mg/kg produced a slight but not statistically significant decrease in the climbing, in response to S' in the 3rd and 4th days. Experiment 4: CAR.
No fraction or drug produced significant changes in the acquisition of
MA 1 mg/kg produced a slight but not significant acceleration of the acquisition
of CAR in the 1st and 2nd experimental days. Experiment 5:
MA in a dose of 1 mg/kg produced a significant increase of the movement
in response to S° on the 2nd and 3rd experimental days (Fig. 3). No qualitative difference was found between the control and the GRg, GNo. 5 or ES treated groups. Experiment 6:
GNo. 5 in a dose of 10 mg/kg and MA 1 mg/kg significantly increased the
number of movements in response to S' on the 3rd day (Fig. 4), but no difference in response to SD was observed between the control and the GNo. 5 or MA treatments.
GNo. 5 in a
dose of 30 mg/kg produced a slight but not significant increase in the number of movements in response to S°. GRg and ES had no effect on DB with either stimuli, though ES in a dose of 0.1 mg/kg produced a slight decrease in the movements in response to S° on the 3rd day. The results of the rotating rod and suspension tests indicated that these fractions had no influence on motor coordination or muscle tone, at least in the above mentioned doses. DISCUSSION The effects of ginseng extract fractions and drugs on the acquisition of CAR were studied in the pole-climbing (Experiment
1) and shuttle-avoidance
(Experiment 4) tests.
No fraction or drug produced any significant change. The effects of drugs on the acquisition of DB in the rats which had learned to avoid shock following signal sounds of 500 Hz at the rate of over 95 % were also studied using the
pole-climbing (Experiment 2 and 3) and shuttle-avoidance (Experiment 6) tests, and also on the acquisition of DB in the naive rats using the shuttle-avoidance test (Experiment 5). GRg produced a significant increase in the acquisition of DB in experiment 2. To obtain the same effect on the acquisition of DB as shown in experiment 2, experiment 3 was performed using a different arrangement between SD and S'.
GRg produced a slight but not significant
increase in the acquisition of DB. GRg given p.o. in the shuttle-avoidance test (Experiments 5 and 6) did not produce any significant change in the acquisition of DB.
These results
indicate that the absorption rate of GRg given p.o. is low and that GRg produces increased alertness or influences the process of learning. GNo. 5, 10 mg/kg produced a significant depression in the acquisition of DB by S° in experiments 3 and 6, but not in experiments 2 and 5.
The effects of GNo. 5 were similar
to those of MA in experiments 3 and 6 but not in experiments 2 and 5.
This may indicate
that GNo. 5 in smaller doses produces an increased alertness not stronger than MA.
In
experiment 2, the effect of GNo. 5-1, an alkaline-soluble fraction from GNo. 5, was similar to that of GNo. 5. This means that CNS-stimulant activity in GNo. 5 is caused by GNo. 5-1.
From these results, it is estimated that two different types of CNS-stimulant activity
are contained in ginseng. The effect of the amphetamines on learning behaviour has been reviewed by Dews and Morse (8). A number of workers have reported that amphetamine facilitated escape response, conditioned avoidance response and discrimination learnings in animals but impairment was seen when larger doses were given (9, 10, 11, 12). In our experiments, MA did not produce an acceleration of the acquisition of CAR and DB in the pole-climbing and shuttle avoidance tests. On the other hand, MA 1 mg/kg produced a significant inhibition of the acquisition of DB to S° in experiments 2, 3, 5 and 6.
There is no doubt that under some
circumstances, impairment in performance and acquisition of DB by methamphetamine would be due to increased alertness or motivation.
The failure in acquisition of DB by MA
in 4 experiments would also be the result of increased alertness since programs on acquisition of DB in these 4 experiments were more complicated and included aversive stimuli. Although several studies have indicated that physostigmine inhibited the performance of conditioned avoidance behaviour (13, 14, 15), smaller doses of physostigmine has been shown to enhance discrimination learning (16, 17, 18, 19, 20). In every experiment herein, ES produced no significant changes in the acquisition of DB. Acknowledgements:
We are grateful to Prof. S. Shibata, Meiji College of Pharmacy,
and Prof. O. Tanaka, School of Medicine, Hiroshima University, for kindly providing the extracts of ginseng root. REFERENCES
1) 2) 3)
PETKOV,V.W.: Uber den Wirkungsmechanisms des Panax Ginseng C.A. Meyer. Arzneim. Forsch. 11, 288-295 (1961) BREKHMAN,1.1. ANDDARDYMOV, I.V.: Pharmacological study of ginseng and related plants. Proc. Pacific Sci. Congr. 11th, 8, 11 (1966) Kim, E.C., CHO, H.Y. AND Kim, J.M.: Effect of Panax ginseng on the central nervous
4) 5) 6) 7) 8) 9) 10) 11) 12) 13) 14) 15)
16) 17)
18) 19) 20)
system. Korean J. Pharmacol. 2, 23-28 (1971) TAKAGI, K., SAITO,H. AND NABATA,H.: Pharmacological studies of Panax ginseng root. Japan. J. Pharmacol. 22, 245-259 (1972) SAITO,H., YOSHIDA,Y. ANDTAKAGI,K.: Effect of Panax ginseng root on exhaustive exercise in mice. Japan. J. Pharmacol. 24, 119-127 (1974) SAITO, H., TSUCHIYA,M., NAKA. S. AND TAKAGI, K.: Effects of Panax ginseng root on conditioned avoidance in rats. Japan. J. Pharmacol. 27, 509-516 (1977) NABATA, H., SAITO, H. AND TAKAGI, K.: Pharmacological studies of neutral saponins (GNS) of Panax ginseng root. Japan. J. Pharmacol. 23, 29-38 (1973) DEWS, P.B. AND MORSE,W.H.: Behavioural pharmacology. A. Rev. Pharmacol. 1, 145-174 (1961) KELEMEN,K. AND BOVET,D.: Effect of drugs upon the defensive behaviour of rats. Acta Physiol. Acad. Sci. Hung. 19, 143 (1965) RAHMANN,H.: Effects of methamphetamine on the memory of golden hamsters. Arch. ges. Physiol. 271, 693-704 (1960) DOMINO, E.F., CALDWELL,D.F. AND HENKE, R.: Effects of psychoactive agents on ac quisition of conditioned pole jumping in rats. Psychopharmacologia 8, 285-289 (1965) SIDMAN,M.: Drug-behaviour interaction. Ann. N.Y. Acad. Sci. 65, 282-302 (1956) CARDO, B.: Effects of thalamic and hypothalamic lesions on conditioning of escape and of tonal differentiation in rats. J. Physiol., Paris 52, 537-553 (1960) DOTY, B.A. AND DOTY, L.A.: Facilitative effects of amphetamine on avoidance condi tioning in relation to age and problem difficulty. Psychopharmacologia 9, 234-241 (1966) PFEIFFER,C.C. AND JENNY,E.H.: The inhibition of the conditioned response and the coun teraction of schizophrenia by muscarinic stimulation of the brain. Ann. N. Y. Acad. Sci. 66, 753-764 (1957) GOLDBERG,M.E., JOHNSON,H.E. AND KNAAK, J.B.: Inhibition of discrete avoidance be haviour by three anticholinesterase agents. Psychopharmacologia 7, 72-76 (1965) PRADHAN,S.N. AND MHATRE,R.M.: Effects of two anticholinesterases on behaviour and cholinesterase activity in rats. Res. Commun. Chem. Path. Pharmacol. 1, 682-690 (1970) BURES,J., BOHDANECK', Z. AND WEISS, T.: Physostigmine induced hyppocampal theta activity and learning in rats. Psychopharmacologia 3, 254-263 (1962) WHITEHOUSE,S.M.: The effects of physostigmine on discrimination learning. Psychophar macologia 9, 183-188 (1966) STRATLON,L.O. AND PETRINOVICH,L.: Post-trial injections of an anti-cholinesterase drug and maze learning in two strains of rats. Psychopharmacologia 5, 47-54 (1963)
OF PANAX
OF SOUND
GINSENG
ROOT ON ACQUISITION
DISCRIMINATION
Hiroshi
SAITO,
Moriyoshi
BEHAVIOUR
TSUCHIYA,
IN RATS
Shinichi
NAKA
and Keijiro TAKAGI* Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan * Department of Pharmacotherapeutics , Faculty of Pharmaceutical Sciences, Tokyo Science University, Shinjuku-ku, Tokyo 162, Japan Accepted
October
23,
1978
Abstract-Pole-climbing and shuttle-avoidance tests were employed to study the acquisition of conditioned avoidance response (CAR) and discrimination behaviour (DB) in male Wistar rats which had been given extracts from Panax Ginseng root intraperitoneally or orally. Neither a lipid soluble fraction (GNo. 5) nor a ginsenoside Rg fraction (GRg) produced significant changes in the acquisition of CAR. GRg given intraperitoneally produced a significant acceleration in the acquisition of DB between a 500 Hz signal sound followed by an electric shock (SD) and a 1000 Hz signal sound without a shock (SJ) in rats which had learned to avoid the shock following S1 at a rate of over 95 %. Small doses of GNo. 5 produced a significant depression in the acquisition of DB.
Several authors
(1-3)
have reported
activity of Panax ginseng root. for fractions
(GNo.
component
fatigued
of ginsenoside
activity.
were compared
neuropharmacological cological
properties
the response avoidance situation
5), from the results
with those of known
was then attempted.
The purpose
the pole-climbing
This may be an indication
of
of both fractions
of their
possible
pharma
a slight shortening
of
and shuttle
of sound stimuli in the avoidance the possible influence of
of CAR and of sound discrimination
and shuttle-avoidance
by blind
but drugs showing similar
(CS) in the pole-climbing
of the present study was to investigate
5 on acquisition
Rgl, the the
activity
the recovery
GRg and GNo. 5 produced
the discrimination
Rg) and lipid
Ginsenoside
from
Interpretation
stimulus
stimulating
is also assumed
(ginsenoside (4).
CNS-stimulants,
were not found.
tests, and GNo. 5 disrupted (6).
(5).
(CNS)
substances
accelerated
to 4 hr oscillation
latency (RL) to the conditioned
GRg and GNo.
(GRg),
Data on the CNS-stimulating
spectra
system
fraction
of blind screening
Rg fraction
states in the mice exposed
CNS-stimulating screening
nervous
of Panax ginseng root, such as the saponin
soluble fraction main
the central
The existence of CNS-stimulating
behaviour
(1313) in
situations.
MATERIALS AND METHODS 1) Pole-Climbing Test The experimental details of the apparatus and the procedure of training were as reported in our previous report (6).
Experiment 1:
Sounds of 500 Hz, which occurred intermittently once a sec and were 0.5
sec in duration, were delivered for 20 sec as CS; the stimulus consisted of sounds only for the first 10 sec and then sounds followed by electric shocks (unconditioned stimulus, 0.1 mA, 35 V, AC) for the remaining 10 sec. This training situation was repeated 10 times during an interval of 2 min per session.
Groups of 10 male Wistar rats (6-7 weeks old) weighing
150-170 g were given each drug and their training carried out in 2 sessions per day at 20 and 100 min after the injection for a week. Experiment 2:
Trained rats which were able to avoid shock stimuli of 500 Hz sounds (CS)
at the rate of over 95 %, were trained to discriminate between sounds of 500 Hz (SD) which were followed by electric shocks and those of 1000 Hz (S°) which were not followed by electric shocks.
The animals were exposed to both SD and S° alternately at intervals of
2 min for 40 min a day, at the same time day for 3 consecutive days.
This procedure was
started from 5 min after the injection of the drugs. Experiment 3:
Trained rats as in experiment 2, were exposed to 5 trials of SD and those
of S° by turns for 40 min a day, at the same time of day for 7 consecutive days.
This pro
cedure was started from 5 min after the injection of drugs. 2)
Shuttle-Avoidance Test The experimental details of the apparatus and the procedure of the training were as
described in the previous paper (7). Experiment 4:
Experiment 4 was designed the same as experiment 1 except for the test
apparatus and the interval of training (1 min). Experiment 5:
Rats in groups of 8 were used.
Naive rats were trained to discriminate between the sounds of 500 Hz (SD)
and those of 1000 Hz (S').
They were exposed to 10 trials of S° at an interval of 1 min,
and then for 5 min without either stimulus.
Ten trials of SD were then delivered at intervals
of 1 min, and after a following 5 min period of no stimulus, trials of S° were started again. The rats were exposed to this situation for 1 hr a day, at the same time of day for 3 consecutive days, 20 min after the administration of drugs. Experiment 6:
Trained rats (7) which had attained a 95-100 % performance level of the
CAR, were exposed to SD and S° alternately an intervals of 1 min for 40 min a day, at the same time of day, for 3 consecutive days.
This procedure was started at 30 min after the
administration. 3)
Rotating rod and Suspension Tests The rotating rod and suspension tests were performed to confirm the dose of drugs
which produced motor incoordination
and/or
muscle relaxation.
The rats were tested
4 times: 10, 40, 70 and 100 min after the i.p. administration, at the same time of day for 7 consecutive days, and 3 times: 40, 70 and 100 min after the p.o. administration for 12 days. 4)
Drug Tested GRg and GNo. 5 from Panax ginseng root were used.
A detailed fractionation
these compounds has been described in our previous report (6).
of
GNo. 5 was separated
into alkaline-soluble (GNo. 5-1) and -insoluble (GNo. 5-2) fractions.
GNo. 5, GNo. 5-1
and GNo. 5-2 were suspended in physiological saline with tween 80. The solution of GRg
was prepared with physiological saline.
Methamphetamine
eserine sulfate (ES) were used as controls.
Drugs were given once a day at the same time
of day, each day preceding the test.
hydrochloride
(MA) and
GRg, GNo. 5, GNo. 5-1 and GNo. 5-2 in doses of
10 and 30 mg/kg were given i.p. in the pole-climbing test. test they were given p.o. from 5 days before the test.
But in the shuttle-avoidance
MA in doses of 0.5 and 1 mg/kg and
ES in doses of 0.03 and 0.1 mg/kg were given i.p. in both tests.
Student's t-test was used
in every experiment for statistical assessment. RESULTS Experiment 1:
No fractions or drugs produced significant changes as compared with the
control in the acquisition of CAR.
GRg in doses of 10 and 30 mg/kg, MA 1 mg/kg and
ES 0.1 mg/kg produced a slight acceleration of the acquisition of CAR in the second session of the first experimental day and in the first or second session of the second experimental day, but this was not statistically significant. Experiment 2:
In the case of 10 mg/kg of GRg, the number of trials in which a rat did not
climb to S° was significantly larger than that in the control on the second experimental day (Fig. 1), but the climbing response to SD was not affected. GRg, 30 mg/kg also produced a similar effect, but it was not statistically significant. MA, 1 mg/kg produced a significant increase in the climbing due to S°. GNo. 5 and ES had no effect on DB to either SD or S°, though GNo. 5 in doses of 10 and 30 mg/kg produced a slight but not significant increase in S' climbing. Experiment 3:
The effects of GRg, GNo. 5, GNo. 5-1, GNo. 5-2, MA and ES on the
acquisition of DB in trained rats were observed repeatedly using a different procedure from that in experiment 2.
In the test using 10 mg/kg of GNo. 5 and GNo. 5-1, the number of
climbings up the pole by S° increased significantly in the 3rd and 4th days (Fig. 2).
No
FIG. 1. Effect of GRg and MA on acquisi tion of DB in the pole-climbing test. a) Percentage of trials of group in which rats did not climb in response to Sa. **: Symbols indicate the significant difference of group between the control and the drug-tested groups (p<0.01, Student's t-test) and * : (p<0.05).
FIG. 2.
Effect of GNo.
5, GNo. 5-1 and MA
on acquisition of DB in the pole-climbing test. See Fig. 1 for expression.
FIG.
3. in test.
Effect naive
of
MA
rats
in
See Fig.
on acquisition the
I for
of
FIG. 4.
DB
shuttle-avoidance
Effect
quisition learned
expression.
ing
sounds
avoidance
of
GNo.
5 and
MA
on
ac
of DB in rats which had to avoid electric shock follow of test.
500
Hz
See Fig.
in
the
shuttle
1 for expression.
difference in the number of trials in which the rat did not climb by SD was observed between the control and the GNo. 5 or GNo. 5-1 treated groups.
One mg/kg of MA also produced
a significant increase in the climbing in response to S° on each experimental day.
GNo.
5-2, GRg and ES had no effect on DB with either SD or S°, though GRg in a dose of 10 mg/kg and ES 0.1 mg/kg produced a slight but not statistically significant decrease in the climbing, in response to S' in the 3rd and 4th days. Experiment 4: CAR.
No fraction or drug produced significant changes in the acquisition of
MA 1 mg/kg produced a slight but not significant acceleration of the acquisition
of CAR in the 1st and 2nd experimental days. Experiment 5:
MA in a dose of 1 mg/kg produced a significant increase of the movement
in response to S° on the 2nd and 3rd experimental days (Fig. 3). No qualitative difference was found between the control and the GRg, GNo. 5 or ES treated groups. Experiment 6:
GNo. 5 in a dose of 10 mg/kg and MA 1 mg/kg significantly increased the
number of movements in response to S' on the 3rd day (Fig. 4), but no difference in response to SD was observed between the control and the GNo. 5 or MA treatments.
GNo. 5 in a
dose of 30 mg/kg produced a slight but not significant increase in the number of movements in response to S°. GRg and ES had no effect on DB with either stimuli, though ES in a dose of 0.1 mg/kg produced a slight decrease in the movements in response to S° on the 3rd day. The results of the rotating rod and suspension tests indicated that these fractions had no influence on motor coordination or muscle tone, at least in the above mentioned doses. DISCUSSION The effects of ginseng extract fractions and drugs on the acquisition of CAR were studied in the pole-climbing (Experiment
1) and shuttle-avoidance
(Experiment 4) tests.
No fraction or drug produced any significant change. The effects of drugs on the acquisition of DB in the rats which had learned to avoid shock following signal sounds of 500 Hz at the rate of over 95 % were also studied using the
pole-climbing (Experiment 2 and 3) and shuttle-avoidance (Experiment 6) tests, and also on the acquisition of DB in the naive rats using the shuttle-avoidance test (Experiment 5). GRg produced a significant increase in the acquisition of DB in experiment 2. To obtain the same effect on the acquisition of DB as shown in experiment 2, experiment 3 was performed using a different arrangement between SD and S'.
GRg produced a slight but not significant
increase in the acquisition of DB. GRg given p.o. in the shuttle-avoidance test (Experiments 5 and 6) did not produce any significant change in the acquisition of DB.
These results
indicate that the absorption rate of GRg given p.o. is low and that GRg produces increased alertness or influences the process of learning. GNo. 5, 10 mg/kg produced a significant depression in the acquisition of DB by S° in experiments 3 and 6, but not in experiments 2 and 5.
The effects of GNo. 5 were similar
to those of MA in experiments 3 and 6 but not in experiments 2 and 5.
This may indicate
that GNo. 5 in smaller doses produces an increased alertness not stronger than MA.
In
experiment 2, the effect of GNo. 5-1, an alkaline-soluble fraction from GNo. 5, was similar to that of GNo. 5. This means that CNS-stimulant activity in GNo. 5 is caused by GNo. 5-1.
From these results, it is estimated that two different types of CNS-stimulant activity
are contained in ginseng. The effect of the amphetamines on learning behaviour has been reviewed by Dews and Morse (8). A number of workers have reported that amphetamine facilitated escape response, conditioned avoidance response and discrimination learnings in animals but impairment was seen when larger doses were given (9, 10, 11, 12). In our experiments, MA did not produce an acceleration of the acquisition of CAR and DB in the pole-climbing and shuttle avoidance tests. On the other hand, MA 1 mg/kg produced a significant inhibition of the acquisition of DB to S° in experiments 2, 3, 5 and 6.
There is no doubt that under some
circumstances, impairment in performance and acquisition of DB by methamphetamine would be due to increased alertness or motivation.
The failure in acquisition of DB by MA
in 4 experiments would also be the result of increased alertness since programs on acquisition of DB in these 4 experiments were more complicated and included aversive stimuli. Although several studies have indicated that physostigmine inhibited the performance of conditioned avoidance behaviour (13, 14, 15), smaller doses of physostigmine has been shown to enhance discrimination learning (16, 17, 18, 19, 20). In every experiment herein, ES produced no significant changes in the acquisition of DB. Acknowledgements:
We are grateful to Prof. S. Shibata, Meiji College of Pharmacy,
and Prof. O. Tanaka, School of Medicine, Hiroshima University, for kindly providing the extracts of ginseng root. REFERENCES
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