EFFECT OF STELAZINE ON AVOIDANCE
LEARNING AND RELEARNING

Thesis for fine Degree of M. A.
MICHEGAN STATE UNIVERSITY

Ralph R. Swarr

1961

 

LIBRARY

Michigan State
University

 

ABSTRACT

EFFECT OF STELAZINE ON AVOIDANCE
LEARNING AND RELEARNING

by Ralph R. Swarr

The effects of the tranquilizing drug, stelazine, on avoidance
learning and relearning were examined in the present study. Five
groups of rats were given 25 avoidance training runs in a modified
Mower-Miller shuttle box, and an additional 25 trial runs were given
48 hours later in the same apparatus. It was found that there was
significantly less avoidance learning among subjects which received
0. 25 mg/kg of stelazine than among control animals, but the drugged
rats were able to make the excape response. When subjects had a
O. 25 mg/kg dosage during the initial learning session, an effect
occurred which caused a reduction of relearning in the later trials
when the animals were not drugged. The normal improvement of
avoidance learning in the relearning trials over the level obtained in
the initial training was inhibited by stelazine, but the compound did
not cause avoidance to drop below a level which had been achieved in

the first 25 trials.

Thesis Advisor: M. Ray Denny, Ph. D.

Approved: flmQr/i %'

Acting I‘I‘he sis Advisdr/

 

Date: 77W] IZJ [75/
(7/ ,

EFFECT OF STELAZINE ON AVOIDANCE
LEARNING AND RELEARNING

BY

Ralph R Swarr

A THESIS

Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

MASTER OF ARTS

Department of Psychology

1961

ACKNOWLEDGMENTS

The author expresses his thanks and appreciation
to Dr. M. Ray Denny, chairman of his thesis committee,
for his guidance and assistance during the planning of the
present research and the preparation of this thesis.
Appreciation and gratitude are also expressed to Dr. Gerald
F. King for his encouragement and constructive advice and
to Dr. Terrence M. Allen and Dr. Charles Hanley for their
helpful suggestions of the analysis of the data.

R. R. S.

ii

TABLE OF CONTENTS

CHAPTER Page

I. INTRODUCTION . . . . . . . . . . . . . . . . 1
II. METHOD . . . . . . . . . . . . . . . . . . . . 10
III. RESULTS. . . . . . . . . . . . . . . . . . . . 14
IV. DISCUSSION . . . . . . . . . . . . . . . . . . 20
V. SUMMARY . . . . . . . . . . . . . . . . . . . 23

REFERENCES 24

iii

LIST OF TA BLES

TABLE Page

1. Summary of Studentized i Ratios of Group-
Session Means Based on the Number of Avoid-
anceResponses................. 15

2.. Summary of t Values Based on the Mean Dif-
ference Betw—een the Number of Avoidance
Responses in Session I and Session II for Each
Subject......................16

A-l? Summary of Avoidance Responses for Subjects
in All Groups for Session I and Session II . . . 27

A-Z. Summary of Avoidance ReSponse Data . . . . . Z8

B-3’i‘ Summary of: Ratios of Group-Session Means
Based on the Response Latencies of All
Subjects.....................30

B-4. Summary of 3 Values Based on the Average
Difference Between the Mean Response Latenc-
ies in Session I and Session II for Each Subject 31

B-5. Summary of Mean Latencies for Subjects in
All Groups for Session I and Session II . . . . 32

C-6l‘ Comparison of Mean Avoidance with Mean
Latencies for _S_s in All Groups for Session I
andSessionII.................. 34

 

¥"A, " "B, " "C" indicate the tables are in the Appendices.

iv

LIST OF FIGURES

FIGURE Page

1. Distribution of Culminative Mean Avoidance
ReSponses from All Groups in Session I and
SessionlI.................... l7

2. Distribution of the Improvement of the Mean
Total Avoidance Responses of Session II Over
Session I for Each Group . . . . . . . . . . . . 19

LIST OF APPENDICES

APPENDIX Page
A. Summary of Avoidance ReSponse Data . . . . 26
B. Summary of Latency Data. . . . . . . . . . . 29
C. Comparison of Avoidance and Latency Data . 33

vi

I. INTRODUCTION

Avoidance learning is learning a response following the onset of
the CS which allows the subject to evade or prevent the occurrence of
the noxious stimulus (US). It is assumed that fear or anxiety is an
important mediator of avoidance. When the organism fails to avoid
and receives the adversive US, the behavior which allows the animal
to terminate the US is called escape behavior. Tranquilizing drugs
have been used to determine if they would affect the animal's ability to
learn avoidance as well as escape. The rationale of such studies
develops from the hypothesis that if tranquilizers bring about reduction
of fear in _S_, then the incidence of avoidance will be reduced.

This type of experiment has been conducted by researchers
interested in contributing quantitative, behavioral data on the pharmaco-
logical profiles of tranquilizing compounds and by researchers seeking
to identify some of the variables relating to the avoidance learning
situation.

Tranquilization is a non- specific term referring to a number of
compounds with varying chemical structures and pharmacological
properties. Pharmacological effects generally assumed to result from
the introduction of tranquilizing agents into an organism include such
conditions as relaxation without anesthetic features (4, 12, 13), good
motor coordination, and ability to be easily aroused (ll). Berger (1)
has divided the tranquilizing agents into the following groups according
to similarity of chemical structure: Phenothiazine derivatives--
chlorpromazine hydrochloride, promazine hydrochloride, triflupromazine

hydrochloride, mepazine, prochlorperazine, perhenazine, trimeprazine,

diethazine, ethopropazine, promethazine, pyrathiazine and stelazine;
Rauwolfia alkaloids and fractions--rauwolfia serpentina, reserpine,
rescinnamine, alseroxylon, and recanescine; Substituted prOpanediols--
meprobamate, phenaglycodal, and mephenesin; Diphenylmethane
derivatives--benactyzine hydrochloride, and hydroxyzine hydrochloride;
and the Ureide and Oxanamide--ectylurea and oxanamide. Brady (3)
reviewed comparative behavioral pharmacological research and noted
the necessity for more systematic, quantitative studies designed to
determine the specific behavioral changes associated with the tranquiliz-
ing agents. Brady cited conditioned avoidance and other fear-type
response patterns as the beginnings of reliable and operationally defin-
able affective behavioral assay techniques.

In studying the effects of tranquilizing agents on conditioned
avoidance behavior, investigators have utilized various techniques to
distinguish those responses which were assumed to be mediated by
emotional factors such as fear or anxiety. Compounds most frequently
investigated from the three main groups (in terms of chemical structure)
have been the Phenothiazine derivative--chlorpromazine, the Rauwolfia
alkaloid--reserpine, and the Substituted propanediol--meprobamate.

Cook and Weidley (5) utilized a pole-climbing apparatus to test
the effect of chloropromazine (and other drugs) on an avoidance learn-
ing reSponse. Their one-foot square testing chamber had a grid floor
which could be electrically charged, a buzzer mounted on the side, and
a rough wooden pole (three-fourths inch in diameter) suspended from
the ceiling. Pre-training trials consisted of a series of shocks (US),
at the rate of five per second, which were delivered concurrently with
the activation of the buzzer (CS) and continued for 30 seconds or until
the S_ terminated the stimuli by climbing the pole (safety area).
Following initial random behavior during the trials, the animals soon

learned to climb the pole, and after 10 to 15 such sessions an avoidance

response was established and they would climb the pole when the buzzer
only was sounded.

The testing procedure consisted of placing the rats in the chamber
for a 30-second accommodation period, after which the buzzer was
sounded for another 30 seconds or until the _5- would climb the pole.

The animal was placed back on the grid, and the US (shock and buzz)
was delivered for 30 seconds or until response terminated by the _S_'s
climbing the pole. Results showed that control rats typically made the
avoidance response within the 30 second intervals before the delivery
of the CS and the US. A chlorpromazine dosage of 10. 5 mg/kg was
found most effective in specifically blocking the conditioned avoidance
response to the CS, but the SS were able to respond to the US. Only at
a dosage of 40 mg/kg did the drug block the US in a few animals.

Other research has contributed to the pharmacological profile
of chlorpromazine. Verhave, it a_.l. , (15) used male rats in research
with an apparatus that consisted of a rectangular box with an attached
movable brass wheel. The grid floor and three metal walls could be
charged electrically (US), and the wheel was the escape area.

A muffled buzzer (CS) was presented seven seconds prior to shock and
continued for five seconds unless response terminated before that time.
Intertrial intervals were varied around a mean of 60 seconds, and _S_s
were run for 160 or 320 trials per session. Results obtained from Es
which received chlorpromazine doses of l. 6 and 2. 5 mg/kg illustrated
that the loss of avoidance reSponses was a function of dosage. Again,
dosages of chlorpromazine which abolished most or all avoidance
responses were noted to have a relatively minor effect on escape
behavior.

Similar selective avoidance results were obtained by Miller, at a_1. ,
(9) with male rats in a two-compartment conditioning apparatus. During

conditioning trials a buzzer was sounded for five seconds or until the

_S_ jumped across a two-inch barrier which separated the two compart—
ments of the apparatus. When the rat failed to avoid within the five-
second period, a shock was presented to the grid floor, and the buzzer
and shock were terminated when the _S_ made the barrier jumping
reSponse. _S_s were given 15 preconditioning trials for 15 consecutive
days prior to administration of the tranquilizing drug variables. During
the chlorpromazine trials ES were given 10 extinction trials in which
the animals did not receive shock if they failed to avoid during the five-
second CS interval. Results indicated that chlorpromazine dosages of
O. 3, O. 6, and 1. 2 mg/kg had respective dosage-related effects on the
decrement in avoidance responding.

Results reported on the effects of reserpine on avoidance and
escape behavior have generally been similar to those findings reviewed
for chlorpromazine. Cook and Weidley (5) used male albino rats in a
pole-climbing technique to demonstrate that reserpine Specifically
blocked the avoidance response to the CS (buzzer) while the animals
remained capable of escaping from the US (shock). This same dichotomy
of avoidance and escape response selectivity was also observed by
Verhave, (it a}. , (15) in a study utilizing a barrier jumping procedure.
Weiskrantz and Wilson (16) reported that reserpine severely depressed
"avoidance" behavior in their study with Rhesus monkeys. Three judges
evaluated _S_ responses to a CS (white noise to which the animals had
been preconditioned) which occurred prior to a noxious US (shock).
While the monkeys could not reSpond in such a way as to avoid experi-
encing the US, the judges evaluated their behavior as any recognizable
change in ongoing behavior. A11_S_s received 10 trials on each of two
days, and three days after the second conditioning day the animals were
tested (without further injections) for retention of the conditioning
response. Ten retention trials were given each day until the _S_s met a

criterion number of avoidance responses. Monkeys who received

reserpine (. 75 mg/kg) showed only slight deviation from "no response"
to the noise during conditioning trials but they responded to the shock.
Also, tranquilized animals required significantly more training to reach
the retention criterion than the control SS required. Smith, e1: a}. , (l4)
and Pfeiffer, (it a_.l. , (10) in studies involving shuttlebox techniques also
found reserpine functions as an inhibitor of the conditioned avoidance
response in monkeys.

Cook and Weidley (5) found that rats receiving meprobamate
responded in a qualitatively different way than _Ss who had received
chlorpromazine or reserpine. Utilizing the same pole-climbing apparatus,
they found rats which received meprobamate did not respond selectively
to the CS and US, but both avoidance and escape behavior were blocked
in many animals. However, the agent blocked these responses only in
neurotoxic dose levels (ataxia and semiprostration) when the animals
could not make the pole-climbing response because of incapacitation of
motor function. Verhave, e_t i1. , (15) reported a high dosage (500 mg/kg)
of meprobamate caused no clear separation of escape and avoidance loss
in male albino rats tested in a wheel-turning apparatus, and animal
activity was at a low level during the trials.

Verhave (15), in a review of his own and other studies, has noted
that the main point of the studies involving chlorpromazine, reserpine,
and other tranquilizers in avoidance learning situations was that the _S_s
were unable to avoid at dosages where they could make the escape
response upon presentation of the US. Verhave concluded that the
selective effect on avoidance and escape responses may have consider-
able generality among the tranquilizers and be independent of the particu-
lar response types and apparatus utilized. Meprobamate remains the
exception to this generalization, for no clear separation of avoidance
and escape loss has been demonstrated for this compound.

Much of the research presently reviewed has been concerned

mainly with the initial effect of the tranquilizing agents on avoidance

learning--both acquisition and extinction--and few of the studies have
been concerned with the effect these compounds might have on retention
or relearning trials given a day or more later when the effects of the
drug have diminished or disappeared. Also, the major assumption
upon which these experiments have been based was that conditioned
fear or anxiety was present and for untranquilized Es served to mediate
in some way learning of the avoidance reSponse. It was assumed that
the tranquilizing agents reduced the incidence of fear or anxiety in
experimental animals and thus made them less able to learn avoidance
behavior. However, these assumptions were subject to criticism, for
the presence of fear or its role in mediating behavior had not been
clearly demonstrated.

Findings from two recent non-drug studies relate to these con-
siderations. Kamin (8) has studied the retention of an incompletely
learned avoidance response. He assumed that if avoidance learning
was interrupted before it was completely mastered, only partial retention
would occur and a retention curve could be plotted. Kamin used hooded
rats in a shuttlebox apparatus. He ran _S_s for 25 avoidance learning
trials and then gave the animals 25 additional retention trials following
delays of 0, 1/2, 1, 6, and 24 hours and 19 days. From his results
he plotted a V-shaped retention curve which indicated that retention
decreased from 0 to 1 hour and then increased from 1 hour to 24 hours
(the ”Kamin Effect"). Kamin interpreted the declining section of the
curve as a function of "forgetting” and the inclining section of the curve
as a function of incubation of the avoidance reSponse. Thus he offered
two independent processes to explain the initial decrease and later
increase of retention as a function of time interval between avoidance
trial sessions. Thus, Kamin's study was a beginning in the attempt to

learn about the retention of the avoidance learning response.

Denny's (7) reinterpretation of the Kamin retention curve was
relevant to the question of the presence of fear or anxiety in the avoid—
ance learning situation. Denny hypothesized that anxiety initially
increased in the interval following the completion of the first 25
avoidance learning trials to a degree that the animal "froze" and was
not able to make the avoidance response in the retention series of
trials. The freezing was the result of the incubation of anxiety which
reached its peak at an interval of approximately one hour and after that
decreased so that the retention curve inclined to a point at 24 hours
that was not significantly different from that of 0 hours. It was hypothe-
sized that if anxiety could be prevented from incubating the Kamin
retention curve could be eliminated.

Denny, with some variations, repeated the Kamin experiment
by utilizing delays of 0, l, and 24 hours. Two different procedures were
employed to inhibit the incubation of anxiety during the one-hour delay
interval. One group of SS was under a reduced food plan for two weeks
and subject to 24-hour food deprivation prior to the trials. These rats
were permitted to eat alone in their home cages during the one-hour
delay. Another group of _S_s remained in the shuttlebox during the inter-
val with the presence of the buzzer or shock (desensitization). Denny
also hypothesized that if animals were given the same amount of shock
received in the initial learning series in trials the following day and
in another situation, then the incubation of anxiety following such second-
day trials would produce the Kamin Effect in further training trials
given one hour later. Data from the procedures supported the incubation
of anxiety hypothesis.

Thus, Kamin's study has introduced the problem of retention
(or relearning) of an avoidance learning response, and Denny's research
has given support to the assumption of the presence of anxiety in the

avoidance learning situation. The role of anxiety, however, remains

obscure. Denny’s results indicated that the incubation of anxiety follow-
ing an initial 25 trials continued to an "excessive" point so that the
animal froze and was unable to make the avoidance learning reSponse.
The present review of other research with tranquilizing agents has
indicated that the removing or blocking of anxiety by the drugs even
more completely reduced the avoidance learning response. An answer
to this paradoxical problem might be that a certain intermediate level
of anxiety is essential for the S to learn avoidance behavior, i. e. ,
tranquilization reduces the level of anxiety too much for learning, and
the incubation of anxiety following an initial learning series of trials
increases the level of anxiety too much for avoidance learning. While
the function of anxiety in avoidance learning is not clear, its demon-
strated presence in such situations makes the use of tranquilizing drug
variables relevant in avoidance learning research.

One purpose of the present study was to contribute behavioral,
pharmacological information about Stelazine, l a Phenothiazine deriva-
tive, so that this relatively unknown tranquilizing agent may be related
to other compounds to which it is similar in chemical structure (e. g. ,
chlorpromazine, etc.) and to tranquilizing drugs in general. Another
purpose was to learn some of the effects of a tranquilizing drug on the

retention (relearning) of avoidance learning behavior.

 

1The only pharmacological information relative to the effects of
stelazine on avoidance behavior found by this experimenter was an un—
published laboratory report from Smith, Kline, and French, the manu-
facturers of the compound. The following comparative dosages
necessary to produce 80% blockage of a conditioned avoidance response
were: stelazine—-7.4 mg/kg, chlorpromazine--l8. 0 mg/kg, and
prochlorpromazine--9. 8 mg/kg. The dosages necessary to produce
20% blockage of an unconditioned response were as follows: stelazine--
l7. 2 mg/kg, chlorpromazine--30. 0 mg/kg, and prochlorpromazine--
O. 8 mg/kg. These comparisons of stelazine with the two compounds
most similar to it in chemical structure, chlorpromazine and prochlor-
promazine, revealed that stelazine is considerably more Specific in its
blocking action than any of the other compounds.

Answers to the following specific questions were sought during
the present research:
(1) Is there an effect of stelazine on initial avoidance learning?

(2) Is there an effect of stelazine on relearning when the original
avoidance learning occurred without tranquilization?

(3) Is there an effect on untranquilized relearning when the
original training occurred under stelazine?

II. METHOD

Subjects

Fifty experimentally-naive hooded rats from the colony of the
Department of Psychology of the Michigan State University and ranging
in age from 158 to 224 days at the beginning of the study were the _S_s.
Prior to and during the research the 37 male and 13 female animals
were housed in cages containing from three to five _S_s of the same sex
and were maintained on ad lib food and water schedules. The rats
were divided randomly into five groups of ten animals each except
that approximately the same ratio of males and females was maintained

in each group.

Apparatus

 

All animals were tested in a modified Mower—Miller shuttle box
which was painted flat black and which had a glass front for observation
by the experimenter. The shuttle box was 36 inches long, 14 inches
high, and 4 inches wide with a hinged ceiling and a grid floor. The
gridway was made of copper rods placed approximately 1/4 inch apart,
and each half of the gridway could be electrically charged independently
of the other half. (The gridway was continuous for the length of the
shuttle box with no barrier in the middle.) A continuous flow of l. 7
milliamps of electricity was supplied directly to the grid rods via a
C. J. Applegate stimulator, and the SS completed the circuit of current
(and thus caused the shock) when they made contact with any two adjacent
grid rods. A seventy decibel electric buzzer (activated by six dry

cells) served as a conditioned response and was attached to the outside

10

ll

of one end of the shuttle box. Three separate toggle switches were
located on a control panel and permitted independent control of each
half of the gridway and the buzzer. The control panel was placed near
the shuttle box and alongside a stopwatch so that the experimenter was
able to observe the animal, operate the switches, and record the data
with a minimum of movement.

A waiting cage, approximately 16 inches long, 6 inches high,
and 6 inches wide was used to house the _S_s in the interval between real
or sham injections and the beginning of the learning sessions. The
interior of the cage was semi-dark because light could enter only from
the wirecloth front, and the cage was placed in a quiet experimental

room.

Procedure

 

The experiment was divided into two sessions so that all _S_s from
every group were given two identical avoidance learning sessions--an
initial incomplete learning series (Session I) including 25 avoidance
learning trials followed 48 hours later by a second relearning phase
(Session 11) including 25 additional trials. The _SS were kept in their
home cages under normal conditions during the inter-session period.

During any given session the _S_ was placed in the shuttle box for
a one minute orientation period before the trials began. The buzzer
(CS) was sounded for five seconds before the shock (US) began and was
response terminated if the animal crossed the midline of the gridway
during that time (avoidance). If the animal failed to avoid, the CS and
US occurred together and were both reSponse terminated when the
animal crossed the midline (escape) or after 35 seconds had elapsed.
The inter-trial interval (time between successive CSs) was one minute.
For those times when _S_ avoided on the initial (one or more) trials of

a series, these trials were not counted as part of the 25 trials so that

12

the first trial of the 25 was one where the rat received the US after
having failed to respond to the CS.

§S from the various groups received different combinations of
the following four types of treatments prior to their Session I and

Session II trials: Sham Injection--the rat was taken from his home cage

 

into an experimental room, held upside-down on the lap of the experi-
menter, rubbed on the ventral midsection with alcohol, punctured
subcutaneously with a hypodermic needle, rubbed again with alcohol,
and then placed in a waiting cage for 15 minutes prior to the beginning

of the session. No Sham Injection-~the animal was taken directly from

 

his home cage, and was immediately ready for the experimental session.

Dosage 0. 25 mg/kg--the _S_ was moved from his living quarters into the

 

experimental room, injected subcutaneously in the ventral midsection
with a solution including 3. 75 mg stelazine per 50 cc. physiological

saline so that each animal received a stelazine dosage of O. 25 mg/kg
of body weight, and placed in the waiting cage for 15 minutes prior to

the beginning of the block of trials. Dosage 0.15 mg/kg--these _S_s

 

received treatment identical to that described for Dosage O. 25 mg/kg
except that the stelazine dosage was 0. 15 mg/kg of animal weight.
All the rats used in the experiment were weighed immediately follow-
ing their initial removal from the home cage prior to the Session I
block of learning trials.

Pre—session treatment combinations for the five groups of _S_s
were assigned as follows: Group A (control) animals received a Sham
Injection before Session I and another Sham Injection prior to Session II;
Group B rats were given No Sham Injection before Session I and Dosage
O. 25 mg/kg before Session II; Group C _S_s received No Sham Injection
and Dosage O. 15 mg/kg prior to Sessions I and II respectively; Group
D animals were given Dosage 0. 25 mg/kg before Session I and Sham
Injection prior to Session II; and Group E rats received Dosage 0. 15

mg/kg and Sham Injection before Sessions I and II respectively.

Group
A (Control)
B

C
D
E

13

Summary of Pre-Session Treatments

Session I
Sham Injection
No Sham Injection
No Sham Injection
Dosage O. 25 mg/kg
Dosage 0.15 mg/kg

Se ssion II

 

Sham Injection
Dosage O. 25 mg/kg
Dosage 0.15 mg/kg
Sham Injection

Sham Injection

III. RESULTS

A Studentized Distribution was used to compare separately the
mean total avoidance reSponses of the groups in Session I and Session II,
and Group B I (No Sham) and Group C I (No Sham) mean responses were
pooled together as one mean because they were obtained from _Ss which
had received identical Session I treatment. The analysis is summarized
in Table l and indicates the following significant differences at the . 05
level (See Table 1, page 15): (l) Rats which received No Sham Injections
in Groups B I and C I made more avoidance responses than SS in Group
D I which were given the larger dosage (O. 25 mg/kg) of Stelazine;
(2) More avoidance responses were completed by control _Ss (Group A I)
who received sham injections than were made by animals in Group D I
which had been administered 0. 25 mg/kg of drug; and (3) During Session
II more avoidance responses were recorded for Group A II (Control)
rats, which received sham injections, than were made by Group D II _S_s
which were given sham injections after having received a 0. 25 mg/kg
dosage during the prior Session I trials. A comparison between the
mean reSponses of Group A I (Control--Sham Injection) and the mean
avoidances of _Ss in the pooled No Sham B I and C I Groups revealed that
these two types of pre-session treatments were not significantly different.
Finally, comparisons of the Group E I mean (_S_s received the ligher
dosage of 0. 15 mg/kg) were not significantly different from the means
of the Groups (A I and B I plus C 1) whose _Ss had received no drug or
the mean of Group D I whose rats received the high dosage (0. 25 mg/kg).
These t_ values thus indicated that the Group E I mean holds an inter-
mediate position somewhere between the No Drug Group (A I and B I plus
C 1) means which are significantly different from the larger dosage
(O. 25 mg/kg) mean of Group D I.

14

15

Table 1--Summary of Studentized: Ratios of Group-Session Means
Based on the Number of Avoidance Responses

 

 

Group-Session 1:}— M .t_ E
gi+c1 :8 3: 0.092 ---
gi+ C I (‘8 3:: 3 09 05
:iJr CI :8 (59.: 1.66 ---
Si (8 ”:2 1.238 _--
3i (8 3:: 2.755 .05
iii :8 Z: 1 517 --_
(Eii 18 1.19:: 0.493 ---
23+ c 11 :8 (3:: 1.211 --_
iii (8 2:: 1.573 -__
33 + E n :8 13:11
Sii (8 1:: Z 87 05
A 11 10 13.9

E11 10 9. 1.2% --_

‘1

 

16

A plot of the culminative mean avoidance reSponses for blocks of
five trials from all groups in Session I and Session II is presented in
Figure 1, page 17. The Session I section of Figure 1 indicates that
the means of Groups A I, B I and C 1, whose _S_s received Control and
No Drug treatments, had progressively higher averages than the inter-
mediate means of Group E (0.15 mg/kg) and the lower means of
Group D I (0. 25 mg/kg). Control Group A II (Sham) means in the
Session II plot were consistently higher than the averages of any of the
experimental groups, and Group C II (0.15 mg/kg) means were greater
than those of Group B 11 (0. 25 mg/kg) whose _Ss received a larger drug
dosage prior to Session II trials. Finally, Group E II and Group D II _Ss,
which were given Session II sham injection treatment similar to that
given to A II control animals, produced response averages which were
correspondingly lower, in terms of the Session I dosages received by
these _Ss, than the Group A II means.

Shown in Table 2 below is a summary oft_ values based on the mean
difference between the number of Session I and Session II avoidance

responses for each S.

Table 2--Summary of t_Values Based on the Mean Difference Between

the Number of Avoidance ReSponses in Session I and Session II
for Each Subject

 

 

Group .1}! P L .13
A 10 4.4 2 14 05
B 10 0.0 0.0 ---
C 10 2.4 1.78 ---
D 10 2.0 1.52 ---
E 10 4.0 2 21 05

 

NUMBER OF CULMINATIVE MEAN AVOIDANCES

H Group A (Sh-Sh)

17

SESSION I

  
  
  
   

 

 

 

9 -- o——o Group B (No Sh-O. 25 MG)
’ H Group C (No Sh-O. 15 MG)
7 " A.--4 Group D (0.25 MG-Sh)
' D---D Group E (0.15 MG-Sh) ID
5 _- //
/
//
1- /
a“
3 r-
”’A
’ ,A’””
1 h—
o. l J
\\ 1 2 3 4 5
15 h
_ SESSION II
13 -
5
ll -'
9 "' ///
F I/
/
7 " 49/
/,’
)- ///
/
5 1— d//
/// /’A
' 4” /’
3 _ _4’ //.A”
h ’l/I, ””‘«’//
l A______,..-_.—A’
0 . 1 1 l 1 l
1 2 3 4 5
BLOCKS OF FIVE TRIALS
Figure 1. Distribution of Culminative Mean Avoidance Responses

from All Groups in Session I and Session II.

18

Significant differences at the . 05 level were obtained between the
Session I and Session 11 means for control Group A (Sham-Sham) and
for Group E whose §S received the 0.15 mg/kg and Sham treatments
respectively prior to each session. The distribution of the improve—
ment of the mean total avoidance responses of Session II over Session I
for each group is graphed in Figure 2, page 19. Group B (No sham-—
0. 25 mg/kg) _S_s showed no improvement, and Group C (No Sham--0. 15
mg/kg) §S with the lighter dosage gave moderate improvement. Finally,
rats in Group D improved only moderately after having the large
dosage and Sham treatments prior to Session I and Session II respectively.
The mean reaction latencies (Appendix B) of the animals were
analyzed in the same way as the avoidance reSponses, and significant
differences were obtained for most of the comparisons which were
found to be significantly different in the avoidance response analysis.
Product-moment correlations of the total avoidance responses with the
total reaction times for each of the fifty _Ss yielded coefficients of . 56
for Session I data and . 67 for Session 11 results, and both of these
coefficients, significant at the . 01 level, indicated a negative corre-
lation between number of avoidances and latency time. Thus, the two
variables appeared to measure essentially the same phenomenon.
Occasionally an animal which failed to make the avoidance
response also failed to escape when the shock was presented. However,
no group included significantly more of these SS than any other group,
and the number of rats in each group who EEO—t. make 25 escapes
during both sessions were as follows: Group A--3, Group B--2,

Group C--2, Group D--4, and Group E--4.

INCREASE IN RESPONSES OF SESSION 11 OVER SESSION I

19

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

r---
P THU
l-TT-
r
i l V
A B C D E
(Sh--Sh) (No Sh-.25) (No Sh-.15) (.25-Sh) (.15-Sh)
GROUPS

Figure 2. Distribution of the Improvement of the Mean Total
Avoidance Responses of Session 11 over Session I
for each Group.

IV . DISCUSSION

Results of the present investigation indicated that the effects of
stelazine in the avoidance learning situation are similar to those of the
other Phenothiazine derivative--chlorpromazine and the Rauwolfia
Alkaloid--reserpine. Consequently it was also found that the effects
of stelazine differ qualitatively from those of the Substituted Propane-
diol--meprobamate as was reported by Cook and Weidley (5) and
Verhave, e_t a_;1., (15).

The reduced number of conditioned avoidance responses of the
drugged _S_s in Session I appear to be a function of dosage as suggested
by Verhave, e_t a_._l. , (15) and Miller, e_t 341. , (9), and the moderate effect
of the smaller dosage indicates an unusual potency of stelazine as
compared with other tranquilizing agents. A search of the literature
revealed no other studies where a tranquilizing compound dosage of
less than 0. 25 mg/kg yielded observable effects. The drug's effect
was a specific blocking of the avoidance response to the buzzer (CS)
while the SS generally were able to make the escape response from the
shock (US); and this selective reaction was accompanied by longer
response latencies. This type of behavior has been reported by others
(5, 15, 16) for both chlorpromazine and reserpine. This specific
blocking of avoidance behavior in drugged _Ss suggests that the reduced
number of avoidance responses (and longer reaction times) may be a
function of some type of reduction (or blockage) of anxiety or fear, and
this reduced anxiety may interfere with the ”excitation" level required
for the organism to make the higher order (or more central) type of
learning response. The rat remains able to perform lower level

(or less central) behavior such as "alerting” to the CS and running to

20

21

escape when the US is presented, although it may take him longer, in
the case of larger dosages, to "decide" to make the escape. The de-
layed reaction times particularly for higher dosage SS suggest that
these animals may have been close to a point of tranquilization which
would have prevented both the higher and lower level types of response,
and further research may show that higher dosages of stelazine will
eliminate the selective responses noted in the present and other
research. The probability that the selective avoidance response is a
function of motor incapacitation or sensory diminution, as suggested
by Brady (3), does not appear tenable because the rapid running escapes
of _S_s from shock, however delayed, indicated serviceable motor co-
ordination (9), and the "alerting" of the §S to the CS and the escapes
from the US showed at least a degree of aural and "pain" sensitivity.
The longer latencies did not appear to result from the Ss' motorial
inability to execute the responses, but rather they may have been a
function of a higher level control which determined how and when to
respond.

Results from the present research also indicated that stelazine
had an inhibiting effect as a function of dosage on the improvement of
learning by those _Ss who made the original learning trials under non-
drugged conditions, but these rats were able to maintain the level of
avoidance learning achieved in the initial session. Again, the _S_s were
inhibited for new learning, and the maintenance of the previous level of
learning might be explained by the hypothesis that once a response has
been learned (acquisition) a lower level type of control is required for
its maintenance. An interesting finding of this study was that _S_s which
received the larger dosage during the initial trials made only moderate
improvement during the relearning series (given without the drug), and
these animals were not able to attain a level of avoidance responding

comparable to that level achieved by non-drugged _S_s during original

22

learning trials. In other words, the O. 25 mg/kg dosage not only in-
hibited the _S's ability to make the avoidance response initially, but
there was some kind of carryover effect which functioned to inhibit

the rat's ability to achieve a level of performance in relearning trials
which is typical for non-drugged animals in initial training sessions.
The experience of not avoiding during the initial trials may have been
impressed (conditioned) at a lower level of control, and this behavior
had to be extinguished before the _S_ could learn to avoid. Thus a greater
number of trials may have been required to extinguish the non-avoiding
behavior (which was established at a lower level of control) when the

animal later was under a non—drugged, higher level type of control.

V. SUMMARY

The present research was designed to study the effects of the
tranquilizing drug, stelazine, on avoidance learning and relearning.
Thirty-seven male and 13 female hooded rats were given 25 avoidance
learning trials in a modified Mower-Miller shuttle box, and these
initial trials were followed 48 hours later by 25 additional relearning
trials. The results indicated that 0. 25 mg/kg of stelazine significantly
reduced initial avoidance learning, correspondingly increased response
latencies, and did not affect _S_s' ability to make the escape response,
and this same dosage when given for the initial trials functioned to
reduce relearning and increase latencies in later trials when the
animals were not drugged. Also, stelazine interfered with the improve-
ment of learning (and the reduction of latencies) of the second series
of trials over the initial trials, but the drug did not reduce the level
of learning below that which had been attained in initial training.

The findings were tentatively interpreted in terms of stelazine's
reduction of an intermediate level of anxiety which may be necessary

for rats to learn avoidance.

23

10.

REF ER ENC ES

. Berger, F. M. The chemistry and mode of action of tranquilizing

drugs. Ann. N. Y. Acad. Sci., 1957, _6_'_7_, 685-700.

 

. Brady, J. V. A comparative approach to the evaluation of drug

effects upon affective behavior. Ann. y. I. Acad. Sci. , 1956,
E, 632-643.

 

. Brady, J. V. A review of comparative behavioral pharmacology.

Ann. N. X. Acad. Sci., 1957, 6_6_, 719-732.

 

. Cook, L. E. Some pharmacological actions of chlorpromazine.

Am. _J_. M. Sci., 1955, 230, 110.

. Cook, L. E. and Weidley, E. Behavioral effects of some pharma-

cological agents. Ann. N. Y_. Acad. Sci., 1957, 6_0, 740-752.

 

. Cook, L. E., Weidley, E., Morris, R., and Mattis, P.

Neuropharmacological and behavioral effects of chlorpromazine.
J. Pharmacol. EXptl. Therap., 1955, 113, ll.

 

. Denny, M. R. The "Kamin effect" in avoidance conditioning.

Amer. Psychol., 1958, 13, 419.

 

. Kamin, L. J. The retention of an incompletely learned avoidance

reSponse. J. comp. physiol. Psychol., 1957, _52, 457-460.

 

. Miler, R. E., Murphy, J. V. and Mirsky, I. A. The effect of

chlorpromazine on fear-motivated behavior in rats. _J. Pharmacol.
exp. Ther., 1957, 120, 379-387.

 

 

Pfeiffer, C. C., Riopelle, A. J., Smith, R. P., Jenny, Elizabeth
and Williams, H. L. Comparative study of the effect of mepro-
bamate on the conditioned response, on strychnine and pestylene-
tetrazol thresholds, on the normal electroencephalogram, and
on polysynaptic reflexes. Ann. N. Y. Acad. Sci., 1957, 67,
734-745. _ " " "—

 

24

11.

12.

l3.

14.

15.

16.

25

Plummer, A. J., Earl, A., Schneider, J. A., Trapold, J. and
Barrett, W. Pharmacology of Rauwolfia alkaloids, including
reserpine. Ann. N. Z. Acad. Sci., 1955, _5_9_, 8-21.

 

Schneider, J. A. and Earl, A. E. Effects of serpasil on behavior
and autonomic regulating mechanisms. Neurology. , 1954, 4,

657-667.

 

Schneider, J. A. and Sigg, E. B. Pharmacologic analysis of
tranquilizing and central stimulating effects. In H. H. Pennes
(Ed.), Psychopharmacology. New York: Hoeber-Harper, 1958.

 

Smith, R. P., Wagman, A. L. and Riopelle, A. J. Effects of
reserpine on conditioned avoidance behavior in normal and brain-

operated monkeys. J. Pharmacol. Exptl. Therap., 1956, 117,
136-141.

 

 

Verhave, T., Owen, J. E. Jr. and Slater, O. H. Effects of various
drugs on escape and avoidance behavior. In H. H. Pennes (Ed. ),
PsychOpharmacology. New York: Hoeber-Harper, 1958.

 

Weiskrantz, L. and Wilson, W. A. Jr. The effects of reserpine on
emotional behavior of normal and brain-operated monkeys.
Ann. 91.x. Acad. Sci., 1955, _f_J_1_, 36-55.

 

APPENDIX A

SUMMARY OF AVOIDANCE RESPONSE DATA

26

27

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Table A-2-Summary of Avoidance Response Data

 

 

Mean

12345678910

12345678910 Mean

Subjects

 

Blocks of

Ses sion 11

Session I

5 Trials

 

1.4
2.4

0.5 0024103031
3.2

0101110010
2124411000

1133245140
3324455330

1.5
1.8
2.7
3.0

2
3
4
5

Group A

1115532000
2045554011

(Sham - Sham)

3.5

4523444450
3515345251

3.4

2044555041

 

1.2
1.7
2.2

1220030004
2520020105

0.5
1.0
1.9
3.0

3.3

0010210010

0230320000
0333450001

2
3
4
5

Group B

1241250205
0440430025

(No Sh- . 25)

2.2

2535352005
2444552205

28

2.4

2340530034

 

1.3
1.7

2.1

3011001043
4030002044

1 1000010000 0.2
2

3
4

1.7
2.3

3003121151
4003204154

Group C

4040013054

(No 511-. 15)

3.0
3.2

5021232555
5041135445

2.2

5030101354
5011143154

2.5

5

 

0.5
0.4

0011000210
1020000010

0000000100 0.1

l

0.6
0.4

0300000201

2
3

Group D
(. 25-Sh)

0.6

0010100220
0343001130

0012000001
0240000100

1.5
1.6

0.7

0135003130

0.8

1330000100

5

 

1.1

0010300043
0002302054
0002502154

0.2

0000100010
0001100013
0011323020
0101514023
0014504024

1

1.6
1.9

2.3

0.6
1.2
1.7
2.0

2
3
4
5

Group E
(.15-Sh)

0211504055
1504403155

2.8

 

APPENDIX B

SUMMARY OF LATENCY DATA

29

30

Table B-3--Summary of t Ratios of Group-Session Means Based on the
ReSponse Latencies of All Subjects

 

 

 

Group-Session 1:1- Ma ,3- E
BI+CI :8 2;: 0.399 -_-
131+ CI :8 122:; 2.668 .025
131+ C I :8 3:3: 1.491 ---
Si 18 12:22 1.294 --_
31 18 13:8: 2‘409 '025
:3; (g 2;: 1.184
(1311 (8 2?; 0.177 --_
211+ C11 :3 5.28 0'7” "-
£11 :8 13:1); 0.476 ---
33+ E11 :3 :2: 3.589 .005
311 :3 g": 3.083 .005
1:11 :8 13:53): 2.566 .025

 

aTime, in seconds, from onset of CS to offset of CS or offset of CS and
US combined.

31

Table B-4--Summary of 1 Values Based on the Average Difference
Between the Mean Response Latencies in Session I and
Session II for Each Subject

 

 

 

Group 11 12 t. E
A 10 1.63 2.278 .025
B 10 0.09 0.13 ---—
C 10 0.68 0.686 ----
D 10 4.71 2.015 .05

E 10 -1.32 -0.215 -—--

 

Table B-5-Summary of Mean Latencies for Subjects of All Groups for Session I and Session II

Mean Latencies

 

 

Group E

Ses I

Group D

Group C

Ses I

Group B

Ses I

Group A

Ses I

 

Se 8 II
Sham

Ses II

Sham

Ses I

Ses II Ses II Ses 11

Rat
Number

.15

.25

.15

No Sh

.25

NoSh

Sham Sham

 

12.0
18.0
18.0

14.0

23.5

8.7

6.5

3.7
13.9

3.4

6.0

3.0
3.0

6.0

9.0

3.0

6.0

10.0 .

6.0

3.0
17.0

7.0
25.5

9.0

3.0

6.0

15.4

5.0

8.0
17.0

5.0
18.0

. 5.0 30.0 12.5

6.0

3.0
12.0

3.0

4.6

32

6.5 6.3

5.0

3.5
13.5

1.5
3.0

6.2

4.5

2.5

6.0

10.0

7.0
16.5

24.0

5.5

5.0
8.4

8.5
13.0

18.0

2.5

2.0

10.5

10

 

10.37

9.05

5.22 6.09 5.41 13.88 .17

5.24

4.53

6.16

2|

 

6.81

6.93

3.34 9.55 4.15

2. 366

2. 896 3. 24

2.328

3.41

 

APPENDIX C

COMPARISON OF AVOIDANCE AND LATENCY DATA

33

34

 

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