Aversive consequences of electroconvulsive shock

Physiology and Behavior. Vol. 5, pp. 631-634. Pergamon Press, 1970. Printed in Great Britain

Aversive Consequences of Electroconvulsive Shock' GORDON

W I N O C U R A N D J O H N A. M I L L S

Department of Psychology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada (Received 7 June 1969) WINOCUR, G. ANDJ. A. MILLS. Aversiveconsequencesofelectroconvulsiveshock. PHYSIOL.BEHAV.5 (6) 631-634, 1970.The behavioral effects of repeated pairings of electroconvulsive shock with a neutral stimulus were examined in a conditioned suppression learning situation. The results confirmed the aversive effects of ECS and showed that fear produced in this way can be as effective as grid shock-induced fear in establishing a conditioned emotional response. There was no support for alternative hypotheses that ECS interferes with normal functioning by inducing conditioned inhibition or increased motor activity. Moreover, it was found that the traumatic effects of ECS are more closely related to the convulsive response itself than to any noxious after-effects occurring during recovery from the seizure. Electroconvulsive shock

Fear

Memory

Conditioned inhibition

P o o r RETENTION of recently acquired habits following d e c . troconvulsive shock (ECS) has been traditionally interpreted in terms of retrograde amnesia caused by a disruption of neural events underlying consolidation of the memory trace [5]. However, this interpretation fails to account for all ECS-induced behavioral changes. As a result, other investigators have advanced hypotheses based on evidence that ECS evokes a strong fear reaction [2], lowered arousal levels [8] and locomotor disinhibition [7, 10]. While there is disagreement regarding the nature of the additional effects, it is significant that this general approach is not necessarily inconsistent with an amnesic interpretation. Recent experiments [1, 7] have clearly demonstrated that ECS is capable of producing both amnesia and disruptive behavior patterns. The present experiment was planned to examine carefully the progressive effects of repeated ECS treatments in a situation which minimized the role ofmemoryloss. Evaluation was also made of a recent suggestion [6] that after-effects associated with post-seizure recovery are of greater behavioral significance than the convulsive treatment itself.

Activity

Noyes food pellet (45 mg) to a receptacle situated 2 in. below and 1 in. to the side of the lever. Number of bar presses were automatically recorded by a counter. A Lafayette Shock Generator (Model 5226) was used to deliver a 1.0 rnA foot shock (FS) for a 1 sec duration. Full grand mal seizures were produced by a 600 V transformer which delivered a 45 m A current for 0.25 sec through wire leads extending from electrodes permanently attached to the rat's ears. The electrodes consisted of aluminum ear tags (LC-24) obtained from the Wahmann Mfg. Co., Baltimore. They were connected to the power source via over-hanging leads permitting the animal unimpeded mobility. The FS and ECS durations were controlled by a Hunter Decade Interval Timer (Model 100, Series D). A 25 W light bulb was hung 1 ft above the centre of the apparatus and served as the CS.

Procedure All animals were reduced to approximately 80 per cent normal body weight and maintained at that level throughout the experiment. On the day before the beginning of shaping, electrodes were permanently attached to the ears of all animals. All subsequent testing was carried out with leads attached whether or not ECS was being administered. Initial training consisted of shaping on a continuous reinforcement (CRF) bar pressing schedule. When the bar pressing habit was well established, daily 9 rain adaptation sessions were instituted. During this phase of training, the CS appeared at the end of 3 min, and remained on for another 3 min. This procedure was repeated until the CS ceased to have a distracting influence on the rat and bar pressing rates was relatively constant across the 3 min periods. Suppression of bar pressing during the CS-on p e r i o d was defined in terms of a Suppression Ratio (SR) which was obtained by dividing the number of b a r presses

METHOD

Subjects The animals were 45 naive, male Wistar rats, weighing about 250 g at the beginning of the experiment. Animals were housed in individual 12 x 9½ x 7 in. wire cages with water available at all times.

Apparatus The testing apparatus was a 9 X 13 X 12in. Plexiglas chamber with a grid floor fitted with a single lever which when depressed with a force of approximately 15 g delivered a single

1This work was supported by Grant APA-287 from the National Research Council of Canada. The assistance of Lorraine R. Smith in conducting the research is gratefully acknowledged. 631

632

WINO(_UR AND MILLS

during the CS-on period by the number of bar presses during the preceding CS-off period plus the number of presses during the CS. Complete failure to press during CS-on would yield a SR of 0.00 while maintaining a constant pressing rate would yield a SR of 0.50. The CS adaptation phase was terminated when animal's SR fell between 0.45 and 0.55 on 2 consecutive days. Animals were than matched with respect to bar pressing rates and divided into 4 major groups for testing. Test sessions for all rats began with a 3 min CS-off period followed by a 3 min CS-on period with food available throughout each session on a CRF schedule. Treatment conditions for the groups were as follows: Group I (n ~ 18). Animals in this group received contingent CS-ECS pairings each day. ECS was administered in the test apparatus coincident with the termination of the CS. Five animals in Group 1 were allowed approximately 30 min to recover in the test apparatus. The rest of the animals were removed during their seizure and recovered in their home cage. Since the rat could be transferred from the test apparatus to its home cage in the adjacent animal room within 30 sec, there was no possibility of even partial recovery in or near the testing area. Group 2 (n .... 6). The UCS for Group 2 was FS which was administered simultaneously with CS offset. The animal was allowed to remain in the apparatus for another 3 min with the CS off and occasionally longer if bar pressing had not resumed within this period. Group 3 (n = 11). In this condition, non-contingent ECS was administered each day outside the test room at least 2 hr after the test session. No UCS was introduced during the test session itself. In order to equate testing conditions as much as possible across groups, 6 animals were removed immediately following CS offset while the other 5 animals were allowed to remain in the test apparatus for an additional 3 min. Group 4 (n = 10). Animals in this group received no UCS at any time. As in Group 3, half the animals were removed immediately following the termination of the CS while the rest received the full 9 min session. All animals were tested once each day for 20 days. In addition to SR's, records were kept of bar press totals during each

3 rain session. Boli counts during the CS-on periods were taken as well and used as an index of emotionality. RE SU L T S

Mean SR's indicating the extent to which bar pressing was maintained during the CS-on period, are presented for all groups in Fig. 1. Since no significant differences resulted from immediate or delayed removal from the apparatus in either Groups l, 3 or 4, data for animals in each group were combined for purposes of presentation. As can be seen from Fig. l, SR's declined rapidly in both Groups 1 and 2. Analysis of Variance applied to these data yielded no between group differences (F < 1, d f ~ 1/22) or interaction effect (F < l, d f = 19/418) although there was a significant Sessions effect (F =- 9.81, dr== 19/418, p < 0.001) indicating the progressive drop in bar pressing. The behavior of animals in both groups was similar in that, beginning at about Session 3, virtually all activity ceased at CS onset and animals remained immobile throughout most of the three minutes CS-on period. In contrast, Group 3 (non-contingent ECS) and Group 4 (CS only) maintained relatively constant bar pressing rates with SR's remaining in the 0.50 range throughout the 20 test sessions. There were no significant between-group differences on the SR measure between Groups 3 and 4. (F = 3.43, df=~ 1/19, p > 0.05) nor were there any changes as a function of repeated testing (F ..... 1.42, d/':= 19/361, p > 0.10). Analysis of variance applied to the SR data of all four groups yielded a highly significant Group ":< Session interaction (F ~-3.51, d f = 57/779, p < 0.001) and Group effect (F -= 28.40, d f = 3/41, p < 0.001). A Duncan Multiple Range Test (DMRT) used to establish differences between specific groups across the 20 test sessions, indicated that both Groups 1 and 2 differed significantly from Groups 3 and 4 on Sessions 3-20 inclusive (all p's < 0.05). Examination of elimination measures during CS-on periods (see Table l) indicated that Group l animals defecated at a significantly higher rate than any of the other groups. M a n n Whitney U-Tests applied to the boll counts indicated that the differences between Group 1 and each of the other groups was

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AVERSIVE CONSEQUENCES OF ECS

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TABLE 1

means at each individual test session. When Group 1 was compared with Groups 3 and 4, significant differences were obtained o n Sessions 6-20 inclusive. The same procedure was applied to Group 2 and, except for Sessions 9, 16 and 20, significant differences were obtained on all sessions beyond the fifth (all p's < 0.05).

MEDIAN NUMBER OF BOLI PER ANIMALOVER ALL TEST SESSIONS Group 1

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DISCUSSION The results clearly indicate that both FS and ECS effectively served as an UCS in producing conditioned suppression of a well established instrumental act. In view of the high defecation rates and freezing behavior exhibited by Groups 1 and 2, the most likely conclusion is that both types of treatment disrupted normal bar pressing by generating a state of incompatible fear which became conditioned to the CS. This conclusion is consistent with the fear hypothesis advanced by Coons and Miller [2]. Moreover, the present results generally support an earlier finding [4] that under certain circumstances ¢motionality engendered by ECS can be of a more intense nature than that engendered by FS. It is important to bear in mind that the present results do not preclude the possibility that ECS also disrupts the consolidation of memory traces [5]. I n d ~ d there is growing evidence that both a strong fear reaction and loss of memory can be produced by ECS [7, 9]. Work by Chorover and Schiller [1] indicates that the memory interference effects of ECS are restricted to those events occurring within seconds prior to the ECS treatment. In the present experiment, the CS always remained on for a period of three minutes before ECS thus making it unlikely that the convulsion could obliterate memory of the stimulus. In any case, it is clear from the present data that the consolidation hypothesis is not directly relevant since animals responded differentially to the CS as a function of ECS pairing. The conditioned inhibition hypothesis of Lewis and Maher [8] has often been proposed to account for behavioral disruptions following ECS. This argument states that ECS

significant at beyond the 0.02 level (two-tailed). It is noteworthy that the defecation rate was five times greater in the CS--ECS group than in the C S - F S group. However, it is also clear that CS--FS pairings resulted in considerable defecation in G r o u p 2 animals as their boli counts were significantly greater than those of Group 4 (U : 13.5, p < 0.05). The effects of non-contingent ECS on defecation rates were also considerable. Rats in G r o u p 3 defecated nearly as much as rats in Group 2 (U = 22.0, p > 0.05) and significantly more than rats in Group 4 (U -~ 25, p < 0.05). In view of the suggestion that ECS may affect response levels [10], statistical analysis was made of bar press totals during the three minute period prior to CS onset (see Fig. 2). It can be seen that on Session 1, all groups pressed at approximately the same rate ( D M R T ; p :> 0.05) indicating that any subsequent disparities could not be related to unequal learning or performance levels. Following Session 1, a progressive decline in response rates was noted in Groups 1 and 2. Analysis of variance applied to the bar pressing totals of Groups 1 and 2 yielded a highly significant Sessions effect (F = 5.69, df= 19/418, p < 0 . 0 0 1 ) but no interaction ( F : 1.09, d r : 19/418, p > 0.30) or between groups effects (F < 1, dr= 1/22). There were no significant differences between the performances of Groups 3 and 4. Since analysis of variance applied to all groups yielded a significant interaction (F : 2.12, d r : 57/779, p ( 0 . 0 0 1 ) and Group effect (F : 4.10,

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TEST SESSIONS

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634

WINOCUR ANI) MILl S

induces a generalized inhibitory state manifested by muscular relaxation and reduced anxiety levels. Repeated CS-ECS pairings would enable the CS alone to evoke these responses which would compete and interfere with other behavioral tendencies. In the present experiment, the freezing associated with conditioned suppression and high defecation rates by Group 1 during CS-on periods would appear to rule out the conditioned inhibition hypothesis which should predict an absence of fear in the test situation resulting in uninhibited (if not enhanced) bar pressing and lowered elimination when compared with Group 2. Vanderwolf [10] suggested that a series of convulsions interferes with central inhibitory mechanisms resulting in facilitation of motor output. Although no specific measures of locomotion were taken, it was obvious that Group 1 animals were much less active during CS-on periods than animals in either Group 3 or 4. It is conceivable that a freezing tendency due to fear and a tendency toward enhanced response facilitation were both operating in conflict, with the freezing response assuming dominance during the highly fearful CS-on period. Extending this argument, one might therefore expect that under non-fear conditions where the likelihood of evoking a freezing response is small, uncontrolled response tendencies would have an increased probability of expression. As a check on this possibility, bar pressing totals for the first three minute periods were analyzed for all groups. It was clear from this analysis that fear evoked by pairing FS or ECS with the CS generalized into the initial three minute no-CS period since response totals in both Groups 1 and 2 progressively declined at significant rates. There were no differences between Groups 1 and 2 but both groups on several occasions pressed significantly less than either Group 3 or 4. Since fear

appears to have generally affected the performance of Groups 1 and 2, attention was therefore focussed on the bar press totals of Groups 3 and 4 to determine if ECS treatment affec ted response output. While animals in Group 3 who received 20 non-contingent ECS's maintained somewhat higher bar pressing rates than Group 4, these differences at no time approached statistical significance. As an additional check on locomotion, a group of non-deprived rats (n 7) from another study that had received a series of 15 ECS treatments and a group of similarly handled but non-shocked rats (n ..... 4} were subjected, prior to experimental testing, to a 30 rain session in an activity wheel. The shocked group displayed an average of 213.3 revolutions compared to 188.5 revolutions by the non-shocked group (t--< 1, dr-: 9). Thus our research has failed to reveal any signs of ECS effects on general locomotion. The present experiment also investigated the suggestion that aversive effects of ECS may be more directly related to recovery from the treatment than to its actual administration [7]. Hartman and Klipple [6] demonstrated that the effects of ECS on a learned response varied as a function of place of recovery although in their experiment, there were no indications of ECS-induced fear or for that matter was there support for any of the established hypotheses. In contrast, Dawson and Pryor [3] varied place of administration and recovery from ECS in evaluating aversive consequences and found place of administration to be the only relevant variable. Our results are consistent with those of Dawson and Pryor in that only contingent CS-ECS pairing was effective in producing conditioned fear whether animals recovered in the test apparatus or were removed and allowed to recover in their home cages.

REFERENCES 1. Chorover, S. L. and P. H. Schiller. Re-examination of prolonged retrograde amnesia in one trial learning. J. comp. physiol. Psychol. 61: 34--41, 1966. 2. Coons, E. E. and N. E. Miller. Conflict versus consolidation of memory traces to explain "retrograde amnesia" produced by ECS. J. comp. physiol. Psychol. 53: 524-531, 1960. 3. Dawson, R. G. and G. T. Pryor. Onset versus recovery of the aversive effects of ECS. Psychonom. Sci. 3: 273-274, 1965. 4. Gerbrandt, L. K. Dissociation of conditioned emotional and avoidance responses due to ECS. Psychonom. Sci. 3" 385-386, 1965. 5. Glickman, S. E. Perseverative neural processes and consolidation of the memory trace. Psychol. Bull. 58: 218-233, 1961.

6. Hartman, A. M. and A. G. Klipple. Effect of place of electroconvulsive shock and place of recovery on conditioned avoidance. J. comp. physiol. Psychol. 61: 138-140, 1966. 7. Hudspeth, W. J., J. L. MeGaugh and C. W. Thomson. Aversive and amnesic effects of eleetroconvulsive shock. J. comp. physiol. Psychol. 57: 61-64, 1964. 8. Lewis, D. J. and B. A. Maher. Neural consolidation and electroconvulsive shock. Psychol. Rev. 72: 225-239, 1965. 9. McGaugh, J. L. and M. C. Madsen. Amnesic and punishing effects of electroconvulsive shock. Science 144: 182-183, 1964. 10. Vanderwolf, C. H. Improved shuttle-box performance following electro-convulsive shock. J. comp. physiol. Psychol. 56: 983-986, 1963.