Effects of paradoxical sleep deprivation on two-way avoidance acquisition

Effects of paradoxical sleep deprivation on two-way avoidance acquisition

Physiology & Behavior, Vol. 29, pp. 581-587. Pergamon Press, 1982. Printed in the U.S.A. Effects of Paradoxical Sleep Deprivation on Two-Way Avoidanc...

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Physiology & Behavior, Vol. 29, pp. 581-587. Pergamon Press, 1982. Printed in the U.S.A.

Effects of Paradoxical Sleep Deprivation on Two-Way Avoidance Acquisition Z. J. M. VAN H U L Z E N A N D A. M. L. C O E N E N

Department of Comparative and Physiological Psychology, University of Nijmegen, Montessorilaan 3, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands R e c e i v e d 26 J a n u a r y 1982 VAN HULZEN, Z. J. M. AND A. M. L. COENEN. Effects of paradoxical sleep deprivation on two-way avoidance acquisition. PHYSIOL. BEHAV. 29(4) 581-587, 1982.--Immediately following 72 hrs of paradoxical sleep (PS) deprivation, Wistar rats were given a shuttle-box avoidance task consisting of 50 trials. At an interval of 6 days retention was assessed through a reaequisition session of 20 trials. In a first experiment, the pendulum technique was employed for PS deprivation and its effects were compared with those produced by the conventional watertank technique. The first technique consists of arousing animals from sleep before PS can arise, by swinging their cages in a way that produces postural imbalance at regular intervals. A moving pendulum just not causing imbalance in the animals served as control for this technique. As control for the watertank technique the large platform was chosen. Shuttle-box avoidance was greatly impaired during the second half of the acquisition session in both platform conditions as compared to both pendulum conditions. A relatively small deficit was found toward the end of the session in both PS deprivation conditions as compared to both control conditions. No differences in avoidance were established during retention testing, suggesting that performance rather than learning deficits occurred during acquisition. In a second experiment, the multiple platform was used for PS deprivation. This modified version of the watertank technique also disrupted performance during shuttle-box avoidance acquisition. However, this effect appeared to be less pronounced than the effect found in the classical platform condition of Experiment 1. It is concluded that the performance deficit induced by both the classical and the multiple platform condition was mainly due to nonspecific effects.

Paradoxical sleep

Paradoxical sleep deprivation

Avoidance conditioning

STUDIES in rodents have shown long-term paradoxical sleep (PS) deprivation to produce variable effects on acquisition of avoidance behaviour (see [17,23] for review). In general, one-trial passive avoidance acquisition and/or short-term retention was found to be unaffected [8, 9, 18, 28], one-way active avoidance acquisition to be impaired [12, 28, 30], and two-way avoidance acquisition to be differentially affected [1,24]. The common perspective of these studies was the question of whether PS plays a role in the recovery or maintenance of the organism's capacity to process and store information [11, 19, 22]. The ambiguous nature of effects provided by this paradigm has prompted investigators either to dismiss the "preparatory" hypothesis of PS or to question the validity of the PS deprivation treatment [2,171. Converging lines of evidence suggest that the effects of PS deprivation on acquisition of avoidance behaviour are mediated, at least in part, by changes in central catecholaminergic activity. Firstly, it has been demonstrated that catecholamine agonists are effective in reversing the disruptive effects of PS deprivation on one-way active avoidance acquisition [12,30]. Secondly, several studies have indicated that the integrity of central catecholamine function is necessary for acquiring or maintaining active avoidance responding, (e.g., [4, 14, 20]). Finally, alterations in brain catecholaminergic activity have been reported as a result of prolonged PS deprivation [16, 25, 26, 29]. A difficulty became manifest in the last type of studies, however, in that config-

Learning and memory

urations of effects were established that reminded most of the authors of a possible role of stress, (cf., [31]). The problem of dissociating between PS deprivation and stress effects still obscures the animal literature on PS deprivation. A plethora of behavioural effects has been reported as a result of PS deprivation, the significance of which is difficult to ascertain (see [6,34]). The one instrumental technique which has commonly been employed for PS deprivation in small animals is the "watertank" technique [13]. Applying another PS deprivation technique may provide an answer as to whether PS deprivation or stress is the major determinant of the reported effects. Recently, the "pendulum" technique has been presented as an alternative of the conventional watertank technique [32]. In a fu-st attempt to reevaluate the effects of PS deprivation on avoidance learning, the two techniques now available were compared as to their effects on two-way avoidance acquisition in rats. Effects were found that were highly dependent on the type of technique used. EXPERIMENT 1 METHOD

Animals Naive male Wistar rats from the WU(SPF63 Cpb) strain [15] were used in this experiment. They were supplied by TNO, Zeist, The Netherlands, at the age of 2 to 3 months.

Copyright © 1982 P e r g a m o n Press---0031-9384/82/100581-07503.00/0

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The animals were singly housed in standard laboratory cages with free access to food and water. The experimental room in which they were maintained was temperature controlled (20-22°C) and artificially illuminated on a 12:12 hr light-dark schedule. White lights (500-600 lux) were on from 21:30 to 09:30 hr and dim red lights (2-3 lux) from 09:30 to 21:30 hr. At least two weeks were allowed to the rats to acclimate to the housing conditions, during which time they were handled almost daily. Immediately prior to the experimental treatment the animals weighed 333__.19 g (mean_SD).

Apparatus PS deprivation was established in the animals by employing the watertank or the pendulum technique. In the first technique the conventional platform situations were utilized. The experimental condition consisted of a small flowerpot placed upside down in the middle of a watertank. The watertank was f'dled with water to a level of approximately 1 cm below the top of the platform. The diameter of the platform measured 6.2 cm. Food and water were provided ad lib from a wire mesh lid covering the watertank. As control condition the same situation was used except that the platform was of greater dimensions (12.8 cm in diameter). In the second technique the situations used were similar to those previously described [33]. Briefly, the experimental condition was a swing varying the position of the animal's cage in a way that produces postural imbalance at regular intervals. The length of the intervals permitted the animals to obtain brief periods of slow wave sleep (SWS) but prevented them from passing to PS. In the control condition a swing was used moving across a distance just not causing postural imbalance in the animal. Two-way avoidance conditioning was carried out in Perspex shuttle-boxes placed in sound-attenuating cabins. The shuttle-box (40x25x45 cm) was divided into two compartments by a barrier extending 3 cm above a grid floor. A tone with a frequency of 4000 Hz and a loudness of 70 dB served as conditioned stimulus (CS). The unconditioned stimulus (UCS) was an electric shock with an intensity of 0.3

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FIG. 2. Mean number of intertrial crossings in the acquistion and retention session of shuttle-box avoidance for small platform (SP), large platform (LP), pendulum experimental (PE), and pendulum control (PC) groups.

mA, delivered through the grids of the box. Training was conducted under dim red light providing 2-3 lux at the floor.

Procedure Rats were randomly assigned to one of four conditions: (a) the small platform, (b) the large platform, (c) the pendulum experimental, and (d) the pendulum control condition (n = 18 per condition). Animals of the third and fourth condition were familiarized with special cages (30 x 25 x 35 cm) that were adapted for the pendulum. Each animal was subjected to its respective treatment for a period of 72 hrs, The treat, ment was completed just before the onset of the dark phase of the illumination cycle (09:30 hr). Immediately thereafter rats were transferred to an adjacent room to train them in shuttle-boxes. The training session consisted of 50 trials of two-way avoidance conditioning. A period of 15 min of free exploration was allowed before the first training trial. Each trial was signalled by the onset of the CS. If the rat crossed to the opposite compartment within 3 sec the CS was terminated. Otherwise the UCS was initiated and continued in conjunction with the CS until an escape response was made. The maximum duration of the UCS was limited to i0 sec. The intertrial interval varied randomly between 48 and 72 sec. After completion of the acquisition session the animals were weighed. Retention was assessed through a reacquisition session after an interval of 6 days, again at the beginning of the dark period. The session consisted of a series o f 20 trials preceded by a 5 min exploratory period. As measures of training the numbers of habituation crossings, avoidances, and intertrial crossings were scored. The number of fecal boli the animals deposited during the acquisition and retention session was also noted. RESULTS For the purpose of statistical analysis the mean numbers of avoidances and intertrial crossings were calculated per ar-

PARADOXICAL SLEEP AND LEARNING PROCESSES bitrary blocks of 10 trials (see Figs. 1 and 2). The mean number of habituation crossings was determined for the entire exploratory period, providing one score for the acquisition and one for the retention session. To analyse these data a multivariate analysis of variance program [7] was conducted according to a 2x2 factorial design. Deprivation treatment and Technique of deprivation were the main factors tested for. With respect to avoidances the analysis showed that both platform conditions exhibited significantly fewer responses on the third to the fifth trial block of the acquisition session, as compared to both pendulum conditions, F(1,68)=8.95, p<0.01; step down F(1,68)=10.98, p <0.01 ; F(1,68)= 18.09, p <0.001 ; step down F(1,68)=9.13, p <0.01; F(1,68) =39.07, p <0.001; step down F(1,68) = 13.74, p <0.001. The analysis further revealed that both deprivation conditions exhibited significantly fewer responses on the fifth trial block of the acquisition session, as compared to both nondeprivation conditions, F(1,68)=6.91, p<0.05; step down F(1,68)=5.58, p<0.05. No significant main effects were found for the two trial blocks of the retention session. The Deprivation treatment x Technique of deprivation interaction effect did not reach significance on any of the trial blocks of acquisition and retention. For intertrial crossings it was shown that both platform conditions exhibited significantly more responses on the second trial block of the acquisition session, as compared to both pendulum conditions, F(1,68)=7.15, p<0.1)l; step down F(1,68)=5.52, p<0.05. Furthermore, both deprivation conditions exhibited significantly more responses on the second and the fifth trial block of the acquisition session, as compared to both nondeprivation conditions, F(1,68)=14.93, p<0.001; step down F(1,68)=13.64, p<0.001; F(1,68)=7.88, p<0.01; step down F(1,68)=8.05, p<0.01. For the two trial blocks of the retention session no significant main effects were established. Because the interaction effect approached significance on the second trial block of the acquisition session, F(1,68)=3.28, 0.07
583 TABLE 1 MEDIAN NUMBER OF FECAL BOLI DEPOSITED BY RATS DURING THE ACQUISITION AND RETENTION SESSION OF SHUTTLE-BOX AVOIDANCE

Acquisition

Retention

Small Platform

0.14 (0.32)*

0.40 (2.15)

Large Platform

0.25 (1.06)

5.50 (1.94)

Pendulum Experimental

5.17 (1.79)

4.90 (2.13)

Pendulum Control

4.75 (2.93)

5.50 (3.18)

*In parentheses: the semi-interquartile range.

not differ significantly from one another. Likewise, no significant difference was established between the small platform and the large platform condition. However, the pendulum experimental appeared significantly different from the pendulum control condition. In pilot work it was noticed that animals exhibited relatively little defecation during shuttle-box avoidance training after their removal from the small platform situation. For this reason the number of fecal boli the animals deposited during the acquisition and retention session was determined for the four treatment conditions (see Table 1). A Kruskal-Wallis nonparametric analysis of variance [27] was conducted in analysing these data. Significant differences among the four conditions were found for the acquisition session, H(3)=21.143, p<0.01, corrected for ties, but not for the retention session, H(3)=7.038, p>0.05, corrected for ties. Subsequent Mann-Whitney U tests (two-tailed) on the acquisition data indicated that the two deprivation conditions were significantly different from one another, U=54.0, p <0.002. A significant difference did not appear between the small platform and large platform condition, U=142.5, p >0.10, and, similarly, between the pendulum experimental and pendulum control condition, U= 144.5, p>0.10. EXPERIMENT 2 In Experiment 1 an impairment of shuttle-box avoidance acquisition was found, for which procedural differences between the watertank and the pendulum technique appeared to be mainly responsible. Given this result it was considered worthwhile to further explore the possibility that stress accompanying the watertank technique was implicated in the disruptive effect. Recently, a new version of the watertank technique has been developed, which apparently induces a lower level of stress [33]. Using this condition for PS deprivation may provide additional insight into the main factor underlying the avoidance deficit. METHOD

Animals

Subjects were 54 naive male Wistar rats from the WU(SPF63 Cpb) strain [15]. They were 2 to 3 months of age

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upon arrival from the supplier (TNO, Zeist, The Netherlands). Prior to the beginning of the experiment rats were similarly housed and treated as the animals of Experiment 1. They weighed 357_+28 g (mean_+SD) at the start of the experimental treatment.

Apparatus The multiple platform condition was used for PS deprivation. It consisted of seven small flowerpots placed upside down in a watertank, one in the centre and the remaining ones around. They were positioned at a distance of 4.5 cm from each other and 4 cm from the wall of the watertank (measured at the top). Each platform measured 6.6 cm in diameter. Food and water were provided in the same way as in the single platform situation (see Experiment 1). In this condition animals can easily move from one platform to another but are unable to utilize more than one platform for sleeping on. In the control condition the centre-pot was replaced by a cup-like platform, consisting of a flowerpot placed upright in a stand with a wire-mesh floor (dia. 10.2 cm) 1.6 cm below the rim of the pot. This platform enables the animal to sleep without danger of falling into the water. Two-way avoidance training was carried out under identical conditions as in Experiment 1.

Procedure Rats were randomly assigned to one of three conditions: (a) the multiple platform, (b) the multiple control, and (c) the home cage condition (n= 18 per condition). They were maintained in their respective condition for a period of 72 hrs. Immediately following the treatment, at the onset of the dark period (09:30 hr), they were tested for acquisition of shuttle-box avoidance and 6 days later for retention. Procedures for conditioning were the same as in Experiment 1. Animals were weighed after completion of the acquisition session. RESULTS Data on the three measures of the shuttle-box avoidance

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FIG. 4. Mean number of intertrial crossings in the acquisition and retention session of shuttle-box avoidance for multiple platform (MP), multiple control (MC), and home cage (HC) groups.

task were determined using the same dependent variables as in Experiment 1. Figures 3 and 4 present the mean numbers of avoidances and intertrial crossings for the three treatment conditions. These data were analysed by conducting a MANOVA-program [7], according to a one-way factorial design. For avoidances significant differences among the three conditions were found on the fourth and the fifth trial block of the acquisition session, F(2,51)=15.27, p<0.001; step down F(2,51)=12.11, p<0,001; F(2,51)=19.55, p<0.001; step down F(2,51)=4.99, p<0.05. No significant differences were established for the two trial blocks of the retention session. Scheff6 post hoc comparisons (a=0.05) revealed that the multiple platform condition exhibited significantly fewer responses than the multiple control condition on the fourth and the fifth trial block of the acquisition session, whereas the multiple control and the home cage condition did not manifest significant differences. With respect to intertrial crossings, the analysis revealed that the three groups were significantly different on the first to the fourth trial block of the acquisition session, F(2,51)=6,61, p<0.01; F(2,51)--7.54, p<0.01; step down F(2,51)=2.82, 0.06

0.15; F(2,51)=5.61, p<0.01; step down F(2,51)=0.29, p>0.75, and on the first trial block of the retention session, F(2,51)=6.00, p<0.01. From Scheff6 post hoc comparisons (a=0.05) it appeared that the multiple platform condition exhibited significantly more responses than the multiple control condition on all data points having a significant overall effect. The comparisons between the multiple platform and home cage condition did not reveal significant differences. With respect to habituation crossings it was found that the three groups were significantly different during the acquisition session only, F(2,51)=5.69, p<0.01. Scheff6 post hoc comparisons (a=0.05) revealed significantly more responses in the multiple platform condition

PARADOXICAL SLEEP AND LEARNING PROCESSES than in the multiple control condition. The latter condition and the home cage condition were not significantly different from one another. The percentage of weight loss was assessed as a rough measure of the amount of stress experienced by the animals during treatment. The mean (+-SD) percentages of weight loss were 3.5__.1.6%, 1.3 + 1.4%, and -0.9___4.5% for the multiple platform, the multiple control, and the home cage condition, respectively. A one-way analysis of variance was conducted on these data revealing significant differences among the three conditions, overall F(2,51) = 31.50, p <0.001. On the basis of Scheff6 post hoc comparisons (a=0.05), a significant difference was found between the multiple platform and the multiple control condition as well as between the multiple control and the home cage condition. As in Experiment 1, a defecation score was determined during the acquisition and retention session for the three treatment conditions (see Table 2). In analysing these data a Kruskal-Wallis nonparametric analysis of variance was conducted. This analysis revealed a significant treatment effect for the acquisition session, H(2) =22.947,p <0.01, corrected for ties, but not for the retention session, H(2)=2.714, p>0.05, corrected for ties. Subsequent Mann-Whitney U tests (twotailed) on the acquisition data indicated that the multiple platform and multiple control condition were significantly different from one another, U=30.5, p<0.002, whereas no significant difference was established between the multiple control and the home cage condition, U= 136.5, p>0. I0. GENERAL DISCUSSION In the present investigation acquisition of shuttle-box avoidance was shown to be highly vulnerable to long-term PS deprivation by means of the watertank technique. In accordance with literature findings [1, 12, 28, 30], this confirms the detrimental nature of this treatment for acquisition of active avoidance behaviour. The selectivity of this treatment, however, is questioned by the finding that the pendulum technique failed to produce a corresponding effect. Apparently, a procedural aspect of the watertank technqiue unrelated to PS deprivation mainly accounts for this effect. The percentage of weight loss during treatment did not clearly differentiate between the watertank and the pendulum technique. This seems to indicate that stress was not of prime importance in disrupting shuttle-box avoidance acquisition. However, since the pendulum technique is based on forced activity, the index of weight loss may not sensitively reflect the amount of stress accompanying this technique. The possibility that stress was still implicated, at least in part, in the disruption of avoidance acquisition may be derived from the observation that the deficit was less severe in the multiple platform condition than in the small platform condition, the first producing a lower percentage of weight loss than the latter (see also [33]). Unexpectedly, a strong dissociation occurred between both PS deprivation techniques with respect to the defecation score. Animals in the small platform, the large platform and the multiple platform condition displayed relatively little defecation during the acquisition session. Consequently, the data on this measure seem to be more in parallel with the impairment of acquisition than those on the measure of weight loss. Rats displaying little defecation during an open field test after exposure to the small platform condition have been characterized as being less emotionally reactive [21]. This interpretation must be viewed cautiously, however, because changes

585 TABLE 2 MEDIANNUMBEROF FECAL BOLl DEPOSITED BY RATS DURINGTHE ACQUISITIONAND.RETENTION SESSION OF SHUTrLE-BOXAVOIDANCE Acquisition

Retention

Multiple Platform

0.25 (0.69)*

4.50 (2.63)

Multiple Control

6.83 (3.33)

6.10 (1.58)

Home Cage

6.17 (1.35)

5.00 (2.19)

*In parentheses: the semi-interquartile range.

in defecation occurring during the immediately preceding PS deprivation treatment might have contaminated the test score. A deterioration of shuttle-box avoidance acquisition, that progressively evolved during the second half of the acquisition session, was found mainly in the two platform experimental conditions. There are several arguments which suggest that changes in central catecholaminergic activity are involved in this effect. Heightened utilization and synthesis of brain catecholamines, especially norepinephrine, has been reported after prolonged PS deprivation (e.g., [26]). Furthermore, acquisition or maintenance of active avoidance responding is generally known to rely on catecholaminergic activity of the brain [10]. Following the PS deprivation treatment, then, utilization of brain catecholamines may be expected to increase further in a learning situation requiring sustained active avoidance responding. It may depend on the degree of imbalance between the processes of synthesis and utilization whether a deficit in active avoidance responding will eventually emerge [3]. PS deprivation has been hypothesized to disrupt catecholamine functioning of the brain in one way or another [I 1]. For this reason it would be particularly detrimental to acquisition of avoidance behaviour [ 12,30]. The findings of the present experiments, however, suggest that nonspecific concomitants of the watertank technique rather than PS deprivation are involved in this kind of deficit (cf., [35]). Inherent in the paradigm of the present experiments is that acquisition of shuttle-box avoidance took place against the background of a particular sleep-waking activity. The characteristics of this activity may largely depend on the degree and selectivity of the preceding PS deprivation treatment. With respect to both PS deprivation techniques a high degree of PS deprivation was pursued, of which loss of SWS is an inevitable consequence. Although not scrutinized, sleep preparatory behaviours during the acquisition session were noticed more frequently in rats of the two platform experimental conditions than in those of the pendulum experimental condition. Therefore, the induction of incipient sleep processes interfering with avoidance performance might have been different in the two PS deprivation techniques. On the basis of the available data, however, it is difficult to determine which of the potentially important factors (PS deprivation, loss of SWS, and perhaps stress) contributed most to the promotion of sleep. Probably, a careful examination of the quality and pattern of sleep-waking ac-

586

VAN H U L Z E N AND COENEN

tivity following PS deprivation would allow a more definite conclusion. Anyway, the rebound of PS produced during the immediate postdeprivation period (i.e., 3 hrs) does not seem to be inferior in the pendulum technique [32] as compared with the watertank technique [36]. The acquisition deficits observed in the present experiments were not reflected in differential retention performances at an interval of six days. This suggests that performance rather than learning or short-term memory processes were affected by the various PS deprivation treatments. The present paradigm, however, does not allow one to conclude that long-term memory processes also remained unaffected. Prolongation of susceptibility to memory disruption by an electroconvulsive shock has been reported after long-term PS deprivation by means of the watertank technique (see [9] for review). In view of the present findings, it is obvious to suggest that nonspecific concomitants of this PS deprivation treatment have rendered the amnestic agent more effective. There remains, however, the theoretical possibility that prolonged PS deprivation specifically impairs processes that enhance resistance to memory disruption (i.e., memory maintenance processes). Increases in the number of crossings were established during the .exploratory period, as well as during intertrial intervals of the acquisition session. This effect predomi-

nantly occurred in the platform experimental conditions. Fhe phenomenon of enhanced locomotor activity following PS deprivation has conventionally been interpreted in terms of the neural excitability hypothesis of PS [5]. In this hypothesis PS deprivation is assumed to heighten neural excitability of the waking state. The present findings cast doubt on the specificity of this phenomenon. Furthermore, they raise the question of whether it is characterized by a concomitant increase in electroencephalographic arousal. In summary, locomotor activity was found to be enhanced and shuttle-box avoidance performance to be severely disrupted following 72 hrs of PS deprivation by means of the watertank technique. Similar effects could not be replicated in using the pendulum technique. Therefore, the possibility that these phenomena are not due to PS deprivation p e r se must seriously be considered.

ACKNOWLEDGEMENT Preliminary reports of this work were presented at the 21st annual meeting of the Association for the Psychophysiological Study of Sleep, held in Hyannis (MA), June, 1981, and at the 5th European Neuroscience Congress, held in Liege, Belgium, September, 198t. We are grateful to Arno Jansen, Henk Maassen and Guus Huis in 't Veld for their assistance in conducting the experiments.

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