- Email: [email protected]
Indices of memory recovery following electroconvulsive shock
Physiology and Behavior, Vol. 9, pp. 783-787. Brain Research Publications Inc., 1972. Printed in U.S.A.
Indices of Memory Recovery Following Electroconvulsive Shock I HENRY E. ADAMS AND K A R E N S. CALHOUN
Department o f Psychology, University o f Georgia, Athens, Georgia 30601
(Received 26 May 1972)
ADAMS, H. E. AND K. S. CALHOUN. Indices of memory recovery following electroconvulsive shock. PHYSIOL. BEHAV. 9(5) 783-787, 1972.-In two experiments recovery of memory for a one-trial passive avoidance task was demonstrated following ECS when a retention ratio was used as an index of retention but not when latency measures were used. In a third experiment, both measures reflected recovery when habituation was controlled and ECS occurred within 10 see of learning. Habituation attenuated the effect of ECS on retention. These experiments indicate that recovery of memory from ECS does occur when assessed by behavioral indices other than latency and that the effects of ECS are probably on the retrieval rather than the storage or consolidation process. Memory
Disinhibition
Electroconvulsive shock
Habituation
studies were conducted to compare latency and another behavioral measure of retention (retention ratio), to test the "sparing" hypothesis of Hine and Paolino, and to examine the relationship of these response measures to the recovery of retention following ECS.
IF A recently learned response is followed within a few seconds by an electroconvulsive shock (ECS), the animal may exhibit a performance decrement when later tested for retention of that response. It has been suggested by some investigators [10] that ECS given during the period of consolidation of the memory trace causes disruption of the engram, resulting in retrograde amnesia. Since ECS presumably disrupts time-dependent processes underlying memory storage, the retention loss is assumed to be permanent. An alternate explanation is that ECS affects retrieval processes, resulting in a performance deficit rather than a memory loss [2]. In this case, the retention loss may be temporary, and different measures of retention may indicate no retention loss. In a previous study by Mendoza and Adams [ 11 ] which has been substantially replicated by Hine and Paolino [ 8 ] it was demonstrated in one-trail passive avoidance learning that ECS causes a retention deficit of the skeletal m o t o r component of the learned fear response (latency) but does not eliminate the conditioned autonomic response (heart rate). Mendoza and Adams suggest that some behavioral measures, e.g., latency, are more susceptible to disinhibition by intense stimuli such as ECS. Hine and Paolino suggest that fear conditioning to generalized environment cues proceeds at a rapid rate but a longer time is required for the formation of association with specific cues in the environment. Consequently, the minimal association of specific cues with foot shock is more susceptible to the effects of ECS than the conditioned generalized fear measured by heart rate. As their behavioral index of retention, Hine and Paolino used latency, a measure commonly used in one-trial learning paradigms. The present
EXPERIMENT 1
Method Fo r t y naive, male, Sprague-Dawley rats approximately 120 days old at the beginning of the experiment were used. The animals had free access to food but were 23 hr water deprived. They were given experimental sessions in a Grason-Stadler operant box which included a stainless steel grid floor through which a scrambled electric shock could be delivered. In the center of the hinged side of the box and 2 in. above the floor was located a metal drinking tube. Whenever the animal licked the tube a drinkometer circuit was completed. A factorial design was used with the two factors being the presence or absence of ECS and the interval between the test-retest period (either 24 or 168 hr). During the first two days each animal was placed in the chamber for 5 min and allowed to drink. Since the animals had previously obtained water from a similar drinking device the only learning involved was locating the metal tube. On the third day differential treatment was initiated. Animals were placed into the chamber to drink for 5 min. Latency was recorded from the time the rat was placed in the chamber and the door was closed until the first lick. At the end of this 5 min period, the next lick resulted in a 1.6 mA, 2 sec foot shock (FS). The animal was then removed from the chamber, earclips were attached to the pinnae,
1This research was supported by USPH Grant MHI 3274 to the senior author. 783
784
ADAMS AND CALHOUN
and an ECS of 35 mA for 0.3 sec duration was administered. In the case of the No ECS FS Group the earclips were simply removed. A short time after the experimental session the animals were allowed to drink for 30 min in their cages. One-half of the animals in each group were given retraining 24 hr later and one-half were given retraining after 168 hr. The retention ratio used was the ratio of lick responses in pretest period (Day 3) to the number of lick responses in the test period (Day 4). When this ratio is approximately 1.00 it indicates the animal is amnestic for FS, and at approximately zero it indicates good retention of FS (few or no lick responses during the test period). Nonparametric statistics were used to analyze the data of all experiments since these data do not satisfy the assumptions of parametric statistics.
/
300" (/) ¢:3 Z
225. W if) Z
150.
t~ Z W _.1 Z
75"
O hi
I--!
24
HRS.
168
HRS.
/
P< .0 I
Results
For the retention ratio the Mann-Whitney U test indicated no significant difference between the No ECS Groups, as shown in Fig. 1. Therefore, these groups were combined and compared with the ECS Groups. The Mann-Whitney U test between the ECS Groups was significant at the 0.05 level of confidence (U = 26) indicating that the 24 hr group was apparently amnestic for FS but that the 168 hr group demonstrated a recovery of retention. The Mann-Whitney U tests between the No ECS Groups and the ECS 24 hr Group (U = 30.5) as well as the ECS 168 hr Group (U = 46) were significant at the 0.01 level of confidence. When the latency measures were analyzed, different results were obtained. The Mann-Whitney U test between ECS Groups was not significant nor was the Mann-Whitney U test between No ECS Groups significant. The ECS Groups were then combined and compared with the combined No ECS Group. The difference was significant at the 0.01 level of confidence (U = 93.5). As far as the latency data are concerned there was no recovery of retention from the effects of ECS. This study indicates, as has been suggested by Mendoza and Adams, that recovery of memory following ECS may depend on the response measure used. EXPERIMENT
2
The second experiment was conducted in order to determine whether the results of the first experiment could be explained by the relatively long interval between FS and ECS, since Chorover and Schiller [6] suggest that an interval of 10 sec or less is necessary for ECS to disrupt the consolidation process. Method
The animals were 40 naive, male, Sprague-Dawley rats approximately 120 days old at the beginning of the experiment. They were given free access to food and were 23 hr water deprived. The design of the experiment was identical to that of the first experiment with the following exceptions: (a) the experimental session was shortened to 3 min since, once the water tube was located, the animals licked at a fairly constant rate; the animals were placed in the experimental chamber and given 2 days training in the box; (b) on the second day the animals were anesthetized and a small hole punched in each ear; 7 days were then
ECS
NECS
1,00.
0 t¢Z OE Z 0 t-Z LU I.-
./'5'
/
P< .05
.50'
nZ .25 LtJ
~
' P < .01
/---N8 ~ .00
ECS
NECS
FIG. 1. Median latencies and retention ratios for Experiment 1. allowed for the pinnae to heal; and, (c) the animals were then placed in the operant box with dress snaps wired to the ECS source placed in their ears. The rats took approximately 8 sessions to adapt to the dress snaps. When the animal reached a criterion of 250 lick responses in the 3 min period, a 1.6 mA FS of 2 sec duration followed the first lick occurring after this period. The ECS (35 mA for 0.3 sec) was administered automatically at exactly 5 sec after the onset of FS. In all other respects Experiment 2 was identical to Experiment 1. Results
Figure 2 shows the results of Experiment 2. With regard to the retention ratio, the Mann-Whitney U test between the No ECS Groups was not significant; therefore, these groups were combined and compared to each of the ECS groups. There was a significant difference at the 0.05 level of confidence between the ECS Groups (U = 26) demonstrating that as far as retention ratio was concerned there was recovery of retention for FS. Both ECS Groups
MEMORY RECOVERY FOLLOWING ECS
B
z 0t j
IBO'
hi ¢/)
Z :>(j
ioo
z
bJ #<[ .J
Z
785 effects of ECS. Considered together, these two studies support the suggestion of Lewis and his colleagues.
I
24
HRS.
EXPERIMENT 3 The third study was designed to reduce the effects of familiarization on ECS as well as to obtain another point in the seven day interval between learning and retention.
168 HRS.
/
P<
Method
50
m
Q UJ
h
F--1 ECS
o i-
n.-
NECS
I'001 .75"
z o iz uJ iw n-
.so,
\
Z .211.
P< .01
The animals were 60 naive, male, Sprague-Dawley rats approximately 120 days old at the beginning of the experiment. They were given free access to food and kept on 23 hr water deprivation. The design was exactly the same as that of the second experiment with the following exceptions: (a) a 72 hr group was added in both the ECS and the No ECS conditions; and, (b) holes were punched in the ears and were allowed to heal prior to beginning the experiment. The animals were initially trained in the operant box for 2 days, as in the first study. On the third day dress snaps containing the leads to the ECS apparatus were attached to the rats' ears. They were then placed in the operant box and on the third lick received a 1.6 mA FS of 2 sec duration. One-half the animals received an ECS of 35 mA for 0.3 sec beginning 5 sec after the onset of the shock. Animals were then immediately removed from the test chamber after ECS treatment. Animals which received no ECS were allowed to stay in the test chamber the same length of time as the ECS animals following FS and were then immediately removed. In this experiment animals were returned for the test session without dress snaps attached to the ears. The response measures used were the latencies and the ratio of lick responses on the second day to the number during the retention test session.
m,,
=E
Results r , ~ N$,,,-~ .0o,
ECS
NEC5
FIG. 2. Median latencies and retention ratios for Experiment 2.
were significantly different from the No ECS Group at the 0.05 level of confidence (U = 53.5 for 24 hr ECS Group and U = 60.5 for 168 hr ECS Group). Using the latency data, neither the Mann-Whitney U test between ECS Groups nor between No ECS Groups was significant. When the ECS Groups were combined and compared with the combined No ECS Groups, the Mann-Whitney U test revealed a significant difference at the 0.01 level of confidence (U = 45.5). This study in general confirms the conclusion of the first experiment that recovery of retention is obtained when retention ratio is the criterion but not obtained when latency measures are used. However, when Experiments 1 and 2 are compared, it is apparent that the degree of amnesia was much greater in Experiment 1 than in Experiment 2 both in terms of latency and the retention ratio. Lewis, Miller, and Misanin [9] have presented evidence that, when rats are familiarized with the experimental situation before passive avoidance training, the familiarization seems to protect the animals from the
Results may be seen in Fig. 3. The differences between retention ratios for the 3 No ECS Groups were not significant as determined by the Kruskal-Wallis one way analysis of variance. However, the differences in retention ratios of the 3 ECS Groups as determined by the Kruskal-Wallis were significant (H = 9.97, d f = 2, p<0.01). These differences were further analyzed using the Mann-Whitney U test. The Mann-Whitney U test indicated no significant difference between the 24 hr and the 72 hr ECS Groups and these were combined and compared with the 168 hr ECS Group. The difference between these combined groups was significant at 0.01 level of confidence (U = 39) indicating that, while no recovery was evident after three days, recovery from ECS had occurred after seven days. The No ECS Groups were combined and compared with the ECS 168 hr Group using a Mann-Whitney U test resulting in z=1.23 which was not significant. The combined No ECS Group was compared with the combined 24 and 72 hr ECS Group and yielded a z=5.27, significant at the 0.01 level. The same tests of significance were used for the latency data and yielded identical results. This experiment indicates that when the interval between ECS and FS is less than 10 sec and familiarization is controlled, recovery of retention is evident using latency scores as well as retention ratio. This is in contrast to the results of the first two experiments.
786
ADAMS AND CALHOUN
i ,o,
I 24HRS . . . . . . ~
N
,_//[
160"
s~
o) •
_.T
.1 I00
D
I'50
•
~ E C S
~'
#
NECS
1.00'
0
.7~"
~ / ~ < .Or ~'
IZ m
P<.OI
-60"
~J rf ~~
i z
.00
I ~'~
ECS
•
i~.,,-i *'
NECS
I
I •
FIG. 3. Median latencies and retention ratios for Experiment 3. DISCUSSION These studies clearly demonstrate recovery of memory when a retention ratio is used as an index of retention, but not always when latencies are used. The behavior of the animals during the retention session in the longer ECS retention interval is revealing. When placed in the apparatus they explore and rapidly find the drinking tube. However, after a few lick responses they immediately stop drinking and freeze. Licking a water tube was a well-learned response since these animals had received water in this manner daily. Cues associated with this response apparently can initiate retrieval of memory for foot shock. Similarly, other environmental cues can initiate retrieval of memory for foot shock. However, the association between environmental cues and foot shock eliciting avoidance of drinking may be poorly learned, particularly in those cases where habituation has not occurred. In passive avoidance
learning, habituation may facilitate the acquisition of a habit, while attenuated habituation interferes with this process. Latency as an index of memory, reflects the initiation of the retrieval process by environmental cues and is more susceptible to the effects of ECS. ECS may interfere directly with the latter retrieval process, as well as indirectly, by attenuating habituation. When habituation and the interval between ECS and learning were controlled, the retention ratio and latency measures both indicated a recovery of retention. This finding further indicates the susceptibility of latency measures to extraneous variables as indicated by Carew [4]. These data emphasize that it should be assumed that an event has modified encoding and/or storage (consolidation) only if all indices of retention show a memory loss. However, if one measure of retention indicates a memory loss and another does not, then a more parsimonious explanation would be in terms of the retrieval process. These data do not support Hine and Paolino's explanation of the failure of ECS to disrupt a conditioned autonomic response, although loss of retention was present using latency as a behavioral index. Since the present investigators as well as Carew have found similar discrepancies between latencies and other behavioral indices of retention, an explanation based on the differences between autonomic and behavioral responses does not seem warranted. The present studies also indicate that familiarization, as Lewis and his colleauges have noted, alters the effects of ECS on retention. Since there does not seem to be any o p era t i o n a l difference between familiarization and habituation, these findings are not surprising in view of the fact that other investigators [3] have found that ECS disrupts habituation. It has been suggested by Carlton [5] that habituation is mediated by a cholinergic system in the brain. Alteration of cholinergic activity causes attenuation of habituation or disinhibition. Adams and his colleagues [1, 7] have presented evidence that ECS disrupts cholinergic activity by a massive release of acetycholine and increased acetycholinesterase activity. Since this retention loss caused by ECS can be eliminated by anticholinergic drugs such as scopolamine, it is suggested that ECS affects the retrieval process by impairing neural transmission. This disinhibition hypothesis would also predict a recovery of memory when cholinergic activity returns to normal functioning. In conclusion, these studies indicated that recovery of memory after ECS does occur when assessed by behavioral measures other than latency. Recovery of memory after ECS may be influenced by many variables, one of which is habituation to the experimental situation. These data support the disinhibition hypothesis suggested by Adams and his colleagues and indicate that the effects of ECS may be on the retrieval rather than the storage or consolidation process.
REFERENCES
1. Adams, H. E,. P. R. Hoblit and P. B. Sutker. Electroconvulsive shock, brain acetylcholinesterase activity, and m e m o r y . PhysioL Behav. 4: 113-116, 1969. 2. Adams, H. E., L. J. Peacock and D. D. Hamrick. ECS and one-trial learning: retrograde amnesia or disinhibition? Physiol. Behav. 2: 435-437, 1967.
3. Barrett, R. J. and O. S. Ray. Attenuation of habituation by electroconvulsive shock. J. comp. physiol. Psychol. 69: 133-135, 1969. 4. Carew, T. J. Do passive-avoidance tasks p e r m i t a s s e s s m e n t of retrograde a m n e s i a in rats? J. comp. physiol. Psychol. 72: 267-271, 1970.
M E M O R Y R E C O V E R Y F O L L O W I N G ECS
5. Carlton, P. L. Cholinergic mechanisms in the control of behavior by the brain.Psychol. Rev. 70: 1 9 - 3 9 , 1963. 6. Chorover, S. T. and P. H. Schiller. Short-term retrograde amnesia in rats. Z comp. physiol. Psychol. 59: 7 3 - 7 8 , 1965. 7. Davis, J. W., R. K. Thomas and H. E. Adams. Interactions of scopolamine and physostigmine with ECS and one-trial learning.Physiol. Behav. 6: 2 1 9 - 2 2 2 , 1971. 8. Hine, B. and R. M. Paolino. Retrograde amnesia: Production of skeletal but not cardiac response gradient by electroconvulsive shock. Science 169: 1224-1226, 1970.
787
9. Lewis, D. J., R. R. Miller and J. R. Misanin. Selective amnesia in rats produced by electroconvulsive shock. J. comp. physiol. Psychol. 69: 136-140, 1969. 10. MeGaugh, J. L. Time dependent processes in memory storage. Science 153: 1351-1358, 1966. 11. Mendoza, J. E. and H. E. Adams. Does ECS produce retrograde amnesia? Physiol. Behav. 4: 3 0 7 - 3 0 9 , 1969.
Indices of Memory Recovery Following Electroconvulsive Shock I HENRY E. ADAMS AND K A R E N S. CALHOUN
Department o f Psychology, University o f Georgia, Athens, Georgia 30601
(Received 26 May 1972)
ADAMS, H. E. AND K. S. CALHOUN. Indices of memory recovery following electroconvulsive shock. PHYSIOL. BEHAV. 9(5) 783-787, 1972.-In two experiments recovery of memory for a one-trial passive avoidance task was demonstrated following ECS when a retention ratio was used as an index of retention but not when latency measures were used. In a third experiment, both measures reflected recovery when habituation was controlled and ECS occurred within 10 see of learning. Habituation attenuated the effect of ECS on retention. These experiments indicate that recovery of memory from ECS does occur when assessed by behavioral indices other than latency and that the effects of ECS are probably on the retrieval rather than the storage or consolidation process. Memory
Disinhibition
Electroconvulsive shock
Habituation
studies were conducted to compare latency and another behavioral measure of retention (retention ratio), to test the "sparing" hypothesis of Hine and Paolino, and to examine the relationship of these response measures to the recovery of retention following ECS.
IF A recently learned response is followed within a few seconds by an electroconvulsive shock (ECS), the animal may exhibit a performance decrement when later tested for retention of that response. It has been suggested by some investigators [10] that ECS given during the period of consolidation of the memory trace causes disruption of the engram, resulting in retrograde amnesia. Since ECS presumably disrupts time-dependent processes underlying memory storage, the retention loss is assumed to be permanent. An alternate explanation is that ECS affects retrieval processes, resulting in a performance deficit rather than a memory loss [2]. In this case, the retention loss may be temporary, and different measures of retention may indicate no retention loss. In a previous study by Mendoza and Adams [ 11 ] which has been substantially replicated by Hine and Paolino [ 8 ] it was demonstrated in one-trail passive avoidance learning that ECS causes a retention deficit of the skeletal m o t o r component of the learned fear response (latency) but does not eliminate the conditioned autonomic response (heart rate). Mendoza and Adams suggest that some behavioral measures, e.g., latency, are more susceptible to disinhibition by intense stimuli such as ECS. Hine and Paolino suggest that fear conditioning to generalized environment cues proceeds at a rapid rate but a longer time is required for the formation of association with specific cues in the environment. Consequently, the minimal association of specific cues with foot shock is more susceptible to the effects of ECS than the conditioned generalized fear measured by heart rate. As their behavioral index of retention, Hine and Paolino used latency, a measure commonly used in one-trial learning paradigms. The present
EXPERIMENT 1
Method Fo r t y naive, male, Sprague-Dawley rats approximately 120 days old at the beginning of the experiment were used. The animals had free access to food but were 23 hr water deprived. They were given experimental sessions in a Grason-Stadler operant box which included a stainless steel grid floor through which a scrambled electric shock could be delivered. In the center of the hinged side of the box and 2 in. above the floor was located a metal drinking tube. Whenever the animal licked the tube a drinkometer circuit was completed. A factorial design was used with the two factors being the presence or absence of ECS and the interval between the test-retest period (either 24 or 168 hr). During the first two days each animal was placed in the chamber for 5 min and allowed to drink. Since the animals had previously obtained water from a similar drinking device the only learning involved was locating the metal tube. On the third day differential treatment was initiated. Animals were placed into the chamber to drink for 5 min. Latency was recorded from the time the rat was placed in the chamber and the door was closed until the first lick. At the end of this 5 min period, the next lick resulted in a 1.6 mA, 2 sec foot shock (FS). The animal was then removed from the chamber, earclips were attached to the pinnae,
1This research was supported by USPH Grant MHI 3274 to the senior author. 783
784
ADAMS AND CALHOUN
and an ECS of 35 mA for 0.3 sec duration was administered. In the case of the No ECS FS Group the earclips were simply removed. A short time after the experimental session the animals were allowed to drink for 30 min in their cages. One-half of the animals in each group were given retraining 24 hr later and one-half were given retraining after 168 hr. The retention ratio used was the ratio of lick responses in pretest period (Day 3) to the number of lick responses in the test period (Day 4). When this ratio is approximately 1.00 it indicates the animal is amnestic for FS, and at approximately zero it indicates good retention of FS (few or no lick responses during the test period). Nonparametric statistics were used to analyze the data of all experiments since these data do not satisfy the assumptions of parametric statistics.
/
300" (/) ¢:3 Z
225. W if) Z
150.
t~ Z W _.1 Z
75"
O hi
I--!
24
HRS.
168
HRS.
/
P< .0 I
Results
For the retention ratio the Mann-Whitney U test indicated no significant difference between the No ECS Groups, as shown in Fig. 1. Therefore, these groups were combined and compared with the ECS Groups. The Mann-Whitney U test between the ECS Groups was significant at the 0.05 level of confidence (U = 26) indicating that the 24 hr group was apparently amnestic for FS but that the 168 hr group demonstrated a recovery of retention. The Mann-Whitney U tests between the No ECS Groups and the ECS 24 hr Group (U = 30.5) as well as the ECS 168 hr Group (U = 46) were significant at the 0.01 level of confidence. When the latency measures were analyzed, different results were obtained. The Mann-Whitney U test between ECS Groups was not significant nor was the Mann-Whitney U test between No ECS Groups significant. The ECS Groups were then combined and compared with the combined No ECS Group. The difference was significant at the 0.01 level of confidence (U = 93.5). As far as the latency data are concerned there was no recovery of retention from the effects of ECS. This study indicates, as has been suggested by Mendoza and Adams, that recovery of memory following ECS may depend on the response measure used. EXPERIMENT
2
The second experiment was conducted in order to determine whether the results of the first experiment could be explained by the relatively long interval between FS and ECS, since Chorover and Schiller [6] suggest that an interval of 10 sec or less is necessary for ECS to disrupt the consolidation process. Method
The animals were 40 naive, male, Sprague-Dawley rats approximately 120 days old at the beginning of the experiment. They were given free access to food and were 23 hr water deprived. The design of the experiment was identical to that of the first experiment with the following exceptions: (a) the experimental session was shortened to 3 min since, once the water tube was located, the animals licked at a fairly constant rate; the animals were placed in the experimental chamber and given 2 days training in the box; (b) on the second day the animals were anesthetized and a small hole punched in each ear; 7 days were then
ECS
NECS
1,00.
0 t¢Z OE Z 0 t-Z LU I.-
./'5'
/
P< .05
.50'
nZ .25 LtJ
~
' P < .01
/---N8 ~ .00
ECS
NECS
FIG. 1. Median latencies and retention ratios for Experiment 1. allowed for the pinnae to heal; and, (c) the animals were then placed in the operant box with dress snaps wired to the ECS source placed in their ears. The rats took approximately 8 sessions to adapt to the dress snaps. When the animal reached a criterion of 250 lick responses in the 3 min period, a 1.6 mA FS of 2 sec duration followed the first lick occurring after this period. The ECS (35 mA for 0.3 sec) was administered automatically at exactly 5 sec after the onset of FS. In all other respects Experiment 2 was identical to Experiment 1. Results
Figure 2 shows the results of Experiment 2. With regard to the retention ratio, the Mann-Whitney U test between the No ECS Groups was not significant; therefore, these groups were combined and compared to each of the ECS groups. There was a significant difference at the 0.05 level of confidence between the ECS Groups (U = 26) demonstrating that as far as retention ratio was concerned there was recovery of retention for FS. Both ECS Groups
MEMORY RECOVERY FOLLOWING ECS
B
z 0t j
IBO'
hi ¢/)
Z :>(j
ioo
z
bJ #<[ .J
Z
785 effects of ECS. Considered together, these two studies support the suggestion of Lewis and his colleagues.
I
24
HRS.
EXPERIMENT 3 The third study was designed to reduce the effects of familiarization on ECS as well as to obtain another point in the seven day interval between learning and retention.
168 HRS.
/
P<
Method
50
m
Q UJ
h
F--1 ECS
o i-
n.-
NECS
I'001 .75"
z o iz uJ iw n-
.so,
\
Z .211.
P< .01
The animals were 60 naive, male, Sprague-Dawley rats approximately 120 days old at the beginning of the experiment. They were given free access to food and kept on 23 hr water deprivation. The design was exactly the same as that of the second experiment with the following exceptions: (a) a 72 hr group was added in both the ECS and the No ECS conditions; and, (b) holes were punched in the ears and were allowed to heal prior to beginning the experiment. The animals were initially trained in the operant box for 2 days, as in the first study. On the third day dress snaps containing the leads to the ECS apparatus were attached to the rats' ears. They were then placed in the operant box and on the third lick received a 1.6 mA FS of 2 sec duration. One-half the animals received an ECS of 35 mA for 0.3 sec beginning 5 sec after the onset of the shock. Animals were then immediately removed from the test chamber after ECS treatment. Animals which received no ECS were allowed to stay in the test chamber the same length of time as the ECS animals following FS and were then immediately removed. In this experiment animals were returned for the test session without dress snaps attached to the ears. The response measures used were the latencies and the ratio of lick responses on the second day to the number during the retention test session.
m,,
=E
Results r , ~ N$,,,-~ .0o,
ECS
NEC5
FIG. 2. Median latencies and retention ratios for Experiment 2.
were significantly different from the No ECS Group at the 0.05 level of confidence (U = 53.5 for 24 hr ECS Group and U = 60.5 for 168 hr ECS Group). Using the latency data, neither the Mann-Whitney U test between ECS Groups nor between No ECS Groups was significant. When the ECS Groups were combined and compared with the combined No ECS Groups, the Mann-Whitney U test revealed a significant difference at the 0.01 level of confidence (U = 45.5). This study in general confirms the conclusion of the first experiment that recovery of retention is obtained when retention ratio is the criterion but not obtained when latency measures are used. However, when Experiments 1 and 2 are compared, it is apparent that the degree of amnesia was much greater in Experiment 1 than in Experiment 2 both in terms of latency and the retention ratio. Lewis, Miller, and Misanin [9] have presented evidence that, when rats are familiarized with the experimental situation before passive avoidance training, the familiarization seems to protect the animals from the
Results may be seen in Fig. 3. The differences between retention ratios for the 3 No ECS Groups were not significant as determined by the Kruskal-Wallis one way analysis of variance. However, the differences in retention ratios of the 3 ECS Groups as determined by the Kruskal-Wallis were significant (H = 9.97, d f = 2, p<0.01). These differences were further analyzed using the Mann-Whitney U test. The Mann-Whitney U test indicated no significant difference between the 24 hr and the 72 hr ECS Groups and these were combined and compared with the 168 hr ECS Group. The difference between these combined groups was significant at 0.01 level of confidence (U = 39) indicating that, while no recovery was evident after three days, recovery from ECS had occurred after seven days. The No ECS Groups were combined and compared with the ECS 168 hr Group using a Mann-Whitney U test resulting in z=1.23 which was not significant. The combined No ECS Group was compared with the combined 24 and 72 hr ECS Group and yielded a z=5.27, significant at the 0.01 level. The same tests of significance were used for the latency data and yielded identical results. This experiment indicates that when the interval between ECS and FS is less than 10 sec and familiarization is controlled, recovery of retention is evident using latency scores as well as retention ratio. This is in contrast to the results of the first two experiments.
786
ADAMS AND CALHOUN
i ,o,
I 24HRS . . . . . . ~
N
,_//[
160"
s~
o) •
_.T
.1 I00
D
I'50
•
~ E C S
~'
#
NECS
1.00'
0
.7~"
~ / ~ < .Or ~'
IZ m
P<.OI
-60"
~J rf ~~
i z
.00
I ~'~
ECS
•
i~.,,-i *'
NECS
I
I •
FIG. 3. Median latencies and retention ratios for Experiment 3. DISCUSSION These studies clearly demonstrate recovery of memory when a retention ratio is used as an index of retention, but not always when latencies are used. The behavior of the animals during the retention session in the longer ECS retention interval is revealing. When placed in the apparatus they explore and rapidly find the drinking tube. However, after a few lick responses they immediately stop drinking and freeze. Licking a water tube was a well-learned response since these animals had received water in this manner daily. Cues associated with this response apparently can initiate retrieval of memory for foot shock. Similarly, other environmental cues can initiate retrieval of memory for foot shock. However, the association between environmental cues and foot shock eliciting avoidance of drinking may be poorly learned, particularly in those cases where habituation has not occurred. In passive avoidance
learning, habituation may facilitate the acquisition of a habit, while attenuated habituation interferes with this process. Latency as an index of memory, reflects the initiation of the retrieval process by environmental cues and is more susceptible to the effects of ECS. ECS may interfere directly with the latter retrieval process, as well as indirectly, by attenuating habituation. When habituation and the interval between ECS and learning were controlled, the retention ratio and latency measures both indicated a recovery of retention. This finding further indicates the susceptibility of latency measures to extraneous variables as indicated by Carew [4]. These data emphasize that it should be assumed that an event has modified encoding and/or storage (consolidation) only if all indices of retention show a memory loss. However, if one measure of retention indicates a memory loss and another does not, then a more parsimonious explanation would be in terms of the retrieval process. These data do not support Hine and Paolino's explanation of the failure of ECS to disrupt a conditioned autonomic response, although loss of retention was present using latency as a behavioral index. Since the present investigators as well as Carew have found similar discrepancies between latencies and other behavioral indices of retention, an explanation based on the differences between autonomic and behavioral responses does not seem warranted. The present studies also indicate that familiarization, as Lewis and his colleauges have noted, alters the effects of ECS on retention. Since there does not seem to be any o p era t i o n a l difference between familiarization and habituation, these findings are not surprising in view of the fact that other investigators [3] have found that ECS disrupts habituation. It has been suggested by Carlton [5] that habituation is mediated by a cholinergic system in the brain. Alteration of cholinergic activity causes attenuation of habituation or disinhibition. Adams and his colleagues [1, 7] have presented evidence that ECS disrupts cholinergic activity by a massive release of acetycholine and increased acetycholinesterase activity. Since this retention loss caused by ECS can be eliminated by anticholinergic drugs such as scopolamine, it is suggested that ECS affects the retrieval process by impairing neural transmission. This disinhibition hypothesis would also predict a recovery of memory when cholinergic activity returns to normal functioning. In conclusion, these studies indicated that recovery of memory after ECS does occur when assessed by behavioral measures other than latency. Recovery of memory after ECS may be influenced by many variables, one of which is habituation to the experimental situation. These data support the disinhibition hypothesis suggested by Adams and his colleagues and indicate that the effects of ECS may be on the retrieval rather than the storage or consolidation process.
REFERENCES
1. Adams, H. E,. P. R. Hoblit and P. B. Sutker. Electroconvulsive shock, brain acetylcholinesterase activity, and m e m o r y . PhysioL Behav. 4: 113-116, 1969. 2. Adams, H. E., L. J. Peacock and D. D. Hamrick. ECS and one-trial learning: retrograde amnesia or disinhibition? Physiol. Behav. 2: 435-437, 1967.
3. Barrett, R. J. and O. S. Ray. Attenuation of habituation by electroconvulsive shock. J. comp. physiol. Psychol. 69: 133-135, 1969. 4. Carew, T. J. Do passive-avoidance tasks p e r m i t a s s e s s m e n t of retrograde a m n e s i a in rats? J. comp. physiol. Psychol. 72: 267-271, 1970.
M E M O R Y R E C O V E R Y F O L L O W I N G ECS
5. Carlton, P. L. Cholinergic mechanisms in the control of behavior by the brain.Psychol. Rev. 70: 1 9 - 3 9 , 1963. 6. Chorover, S. T. and P. H. Schiller. Short-term retrograde amnesia in rats. Z comp. physiol. Psychol. 59: 7 3 - 7 8 , 1965. 7. Davis, J. W., R. K. Thomas and H. E. Adams. Interactions of scopolamine and physostigmine with ECS and one-trial learning.Physiol. Behav. 6: 2 1 9 - 2 2 2 , 1971. 8. Hine, B. and R. M. Paolino. Retrograde amnesia: Production of skeletal but not cardiac response gradient by electroconvulsive shock. Science 169: 1224-1226, 1970.
787
9. Lewis, D. J., R. R. Miller and J. R. Misanin. Selective amnesia in rats produced by electroconvulsive shock. J. comp. physiol. Psychol. 69: 136-140, 1969. 10. MeGaugh, J. L. Time dependent processes in memory storage. Science 153: 1351-1358, 1966. 11. Mendoza, J. E. and H. E. Adams. Does ECS produce retrograde amnesia? Physiol. Behav. 4: 3 0 7 - 3 0 9 , 1969.