Time-dependent improvement of performance on appetitive tasks in mice

BEHAVIORAL BIOLOGY, 11, 89-100 (1974), Abstract No. 3202

Time-Dependent Improvement of Performance on A p p e t i t i v e T a s k s in M i c e 1

ROBERT JAFFARD, CLAUDE DESTRADE, BERNARD SOUMIREU-MOURAT, and BERNARD CARDO

Laboratoire de Psychophysiologie, Institut de Biologie Anirnale, Avenue des Facultds, 33405-Talence, France Three experiments were carried out to study improvement of performance with time on appetitive tasks in BALB/c mice. Experiments 1 and 2 showed that a 24-hr interval between learning sessions significantly improves performance. It seems that there was a curvilinear relationship between this improvement and the 1st learning session duration. Experiment 3 showed that improvement is time-dependent and occured between 1 and 12 hr after the end of the learning session. These results confirm the hypothesis according to which the consolidation phase should be more an elaborative process than a simple fixing.

Numerous experiments show that, under certain conditions, retention depends on the delay between acquisition and the retention session (Bunch & Magdsick, 1933 quoted by Munn, 1950; Anderson, 1940; Kamin, 1957, 1963; Gabriel, 1968, 1970; Huppert & Deutsch, 1969; Geller et al., 1970; Jarvik, 1972). This phenomenon, however, has almost always been studied on avoidance learning, and the results obtained more often than not show a drop in performance. In our laboratory, we have frequently observed that in appetitive learning a delay of 12 or 24 hr between a partial acquisition and a retention session significantly improves performance. Moreover, certain treatments considered to be effective in producing amnesia were capable of suppressing these improvements, both on operant conditioning in a Skinner box, and on discriminative learning in a Y maze (Jaffard & Cardo, 1970; Soumireu-Mourat & eardo, 1972). In order to investigate this phenomenon in greater detail, three experiments were carried out. In experiment 1 we studied the performance improvement after a 24-hr delay following an initial session of varying duration in a continuous reinforced lever-press conditioning. Experiment 2 was 1Supported by Grant No. 71.7.2871 of Dglggation Gdndrale ~ la Recherche Scientifique et Technique. 89 Copyright © 1974 by Academic Press, Inc. All rights of reproduction in any form reserved.

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carried out in order to test, in the same way, the performance improvement in a discriminative lever-press conditioning. Finally, experiment 3 was carried out in order to study the relationship between the performance improvement and the intersession delay.

EXPERIMENT 1 Method Subjects. Eighty male mice of the BALB/c strain, 60 to 80 days old at the beginning of the experiment, were used. Outside of the learning sessions, all the animals lived in a climatised house (21°C) maintained on a light-dark cycle of 12 hr of light and 12 hr of dark. Eight days prior to the beginning of the learning tests, the animals were put in individual cages with ad libitum feeding and watering. Apparatus. The apparatus used in these experiments has already been described (Destrade et al., 1973). The Skinner box (0.14 m square and 0.18 m high) differs from the usual dispensers on two points: The lever and the food cup are separated by a 0.05 m long partition; the mouse thus has to make a turn either to press the lever or to find food. The animal is always introduced into or withdrawn from the Skinner box via a waiting box, which communicated by a sliding partition. The dispenser was programmed in continuous reinforcement (CRF, 6-rag pellets). All the lever-presses were registered on a pen-recorder. Procedure. Once isolated, all the animals were handled daily for a few minutes in order to attenuate their emotional reactions. As the learning sessions took place on the 9th and 10th days following this isolation, a food deprivation schedule was applied as from the 5th day: 4 g on the 5th day, 3 g on the 6th day, 2 g on the 7th day; on the 8th day, the rations were individually adjusted so that the weight losses reached 17 to 19%onthe 9th day (18.5 + 0.1%). The animals underwent no pretraining or shaping. The animals were randomly assigned to 8 groups of 10 subjects, each group differing from the other by the duration of the 1st session. The group Gs remained 5 rain in the box, and each of the following groups, G1 o l G1 s l G 2 o , G 2 s , G 3 o , G 3 s , and G4o, remained in the box 5 rain longer than the previous group. Twenty-four hours after the 1st session, all the animals were submitted to a 2nd session of 30 rain. Thirty min after the end of the 1st session all the animals were given a food ration of between 2.5 and 3 g, which was individually adjusted so that their weight at the beginning of the 2nd session was identical to their weight at the 1st session. This procedure has made it possible for us to evaluate the effect of a 24-hr interval. For animals having received the same amount of

IMPROVEMENT OF PERFORMANCE WITH TIME

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learning, we compared the performances recorded 24 hr afterwards with those recorded immediately afterward. In order to eliminate effects other than those due to the 24-hr interval, several precautions were taken: On the one hand, the learning tests took place during those periods when the circadian acitvity does not undergo any major variation (8 hr 30 min to 12 hr 30 min in the morning and 16 hr to 19 hr in the afternoon). We counterbalanced between the groups the effects of the time and the day of learning, by testing animals of the same group at different times during the day, and animals of different groups on the same day. On the other hand, in order to check that the interruption as such had no effect on the performances in the 1st session, the learning was interrupted for 2 min, 5 min before the end of the 1st session (when the animals went into the waiting box). Finally, in order to make the food needs between the end of the 1st session and the beginning of the 2nd the same, 30 min before the beginning of the 2nd session, all the animals were given an amount of food equivalent to the amount they had consumed in the 1st session. Results

Table 1 summarizes the results obtained. First session. Generally all the pellets liberated were consumed immediately. An analysis of variance was carried out for each 5-min block. The random assignment of subjects to groups appeared to be satisfactory; the between group F for lever-pressing was less than unity (F from 0.01 to 0.46). Moreover, this result shows that the 2-rain interruption has no effect on the performances. One notes a significant drop in performance during the 2nd and 3rd blocks in relation to the 1st block ( P < 0.001 in each case). The lever and the food cup being separated by a partition this drop could be explained by two factors: A decrease in the short-term exploratory activity, and a localisation of the animals around the food cup. These two factors would bring about a decrease in lever-presses. Second session. The performances are shown on the right-hand side of Table 1. One notes that all the animals reach an asymptotic performance level with greater or lesser precocity. On the other hand, in the first 5-min block of this 2nd session, performances vary greatly according to the groups. It is these performances which best express the effect of the 24-hr interval. We thus compared these performances of the first 5 min of the 2nd session to the mean performances of the different groups in the 1st session, in such a way that the amount of learning was the same in both cases. Seven comparisons were possible. They are shown in Table 2, which also sets out the statistical significance of the differences observed. One can note that for all the comparisons carried out, except for the last, the performances are statistically greater after a 24-hr interval, whilst the amount of learning remains the same.

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70

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93

TABLE 2 Evaluation of the 24-hr Delay Effect on CRF Lever-Press Conditioning Performances for Different Training Levels Lever presses (M -+ SEM) of the pooled groups during a 5-min block (in brackets) of the 1st session (0-min delay)

G10 to G40 G15 to G4o G2otoG40 G2s to G4o G3o to G4o G35 & G40 G4o

(2ndblock): 4.8 -+ 0.1 (3rdblock): 4.4 -+0.2 (4thblock): 6.7-+0.3 (5th block): 10.9 -+0.7 (6th block): 13.6 +- 0.7 (7th block): 17.7 -+0.8 (8th block): 20.4 +- 0.8

Mean lever-presses and SEM during the 1st 5-rain block of the 2nd session (24-hr delay) Gs : 5.9 -+0.3 Glo: 9.6 + 0.5 Gls :11.7 -+1.3 G2o: 15 +- 1.1 G2s: 19.9 +- 2.6 G30:23.2 _+1.4 G3s : 21 +-0.8

P

< 0.01 < 0.001 <0.001 = 0.01 < 0.01 < 0.01 N.S.

It also appears that this improvement is more marked for partial learning of average duration than for brief or long partial learning. However, given the type of behavior studied, this improvement could result from nonspecific factors, such as modifications of the general level of activity in the Skinner box. In order to meet this objection, we studied the influence of a 24-hr interval on a discriminative operant conditioning. Since that the classic analysis of such learning implies the development of an excitatory gradient around the positive stimulus and the development of an inhibitory gradient around the negative stimulus, this type of behavior seemed sufficient to answer the objection raised.

EXPERIMENT 2

Method Subjects. Fifty male mice of the BALB/c strain, 60 to 80 days old at the beginning of the experiment, were used. Four days before the start of the food deprivation procedure, they were placed in individual cages and treated according to the previously described procedure. Apparatus. The food dispenser was the same as that described in the 1st experiment. For discrimination learning, the positive stimulus (SD) was a light and a buzzer presented simultaneously. The buzzer (70 dB)was mounted above the Skinner box. Illumination inside the box (250 lux) was given by a 6.5 W lamp mounted outside the box opposite the lever. The negative stimulus (S A) was provided by a simple, low intensity diffuse illumination (10 lux). During learning, the SD and S A periods were presented alternately during successive

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10-min blocks. Each period varied between 30 and 75 sec (mean duration 50 sec). Each block included a total of 5 min of testing under SD, with all bar presses reinforced, and a total of 5min under SA with no bar press reinforcement. Performance was individually calculated and expressed as a discrimination ratio (SD/SD + S A; Leaton & Kreindler, 1971), where SD was the number of responses during the reinforced 5 min of a 10-min block and S A the number of bar press responses during the nonreinforced 5 rain of the same block. Procedure Pretraining. As from the 5th day, and for 4 days following their isolation, the animals were subjected to a deprivation procedure very similar to that of the 1st Experiment. On the 9th day, they were subjected to a 30-min pretraining session under CRF. On the 10th and l l t h days, two 10-min sessions completed this pretraining. At these sessions, the animal weight-losses were maintained constant (15 to 17% of the ad libitum weight). Learning. The 1st learning session took place the following day (12th day). The day before, all the animals were given 2 g of food; their weight loss at the time of this first session was 18 to 20% (19.0-+ 0.2%). The subjects were randomly assigned to 4 groups: The duration of the session was fixed at 10 min for the 1st group G10 (N = 15), at 20 min for the 2nd group G2o (N = 15), at 30 min for the 3rd group G3o (N= 10),andat 40 min for the 4th group G4o (N = 10). Twenty-four hours later all these animals were submitted to a second session of 10 rain. Thirty minutes after the end of the 1st session, the animals were given 2.8 to 3 g of food, in order that their weight should be the same as their weight at the 1st session. As in the 1st experiment, we counter-balanced the effects of the time and the day of the experiment between the groups. In the same way, in order to evaluate the effect of the 24-hr interval, for animals having received the same amount of learning, we compared the performances recorded 24 hr afterwards to those recorded immediately afterward. Results

As in the 1st experiment, we observed no difference in the 1st session in the performance recorded for each group (F from 0.28 to 0.79). This result permits comparisons aimed at evaluating the influence of the 24-hr interval. Table 3 summarizes these comparisons and makes it possible to note on the one hand a general improvement after a 24-hr delay, and, on the other hand, a greater improvement for an average degree of learning (20 min) than for the other two degrees (10 and 30 rain). These results show that the performance gain observed on CRF leverpress conditioning can be obtained on a discrimination learning. Thus, the

95

IMPROVEMENT OF PERFORMANCEWITH TIME TABLE 3 Evaluation of 24-hr Delay Effect on Discriminative Operant Conditioning Performances for Different Training Levels Discrimination ratio (M + SEM) of the pooled groups during a 10-rain block (in brackets) of 1st session (0-min delay)

Discrimination ratio (M +-SEM) during the first 10-min block of the 2nd session (24-hr delay)

G20 to G4o G3o and G4o G4o

G10 0.567 + 0.018 G20 0.715 -+0.021 G30 0.783 -+0.028

(2nd block) 0.481 -+0.012 (3rd block) 0.565 -+0.015 (4th block) 0.679 -+0.022

< 0.01 < 0.001 fi/0.01

improvement noted in the 1st experiment cannot be attributed to nonspecific modifications in the animals' behavior. The 3rd experiment aims at plotting the performance level curve in function of the intersession delay. For this experiment, the duration of the 1st session was chosen as being equal to 20 rain, this period corresponding to the maximum effect observed after a 24-hr delay.

EXPERIMENT 3

Method Subjects. Sixty-nine mice of the BALB/c strain, 60 to 80 days old at the beginning of the experiment, were used. They were prepared according to the previously described procedure. Apparatus. The apparatus was the same as that described in the 2nd experiment. Procedure. The animals were submitted to a pretraining identical to that of the 2nd experiment; they were then randomly assigned to 7 groups and subjected to a 1st session of 20 min duration. They were finally subjected to a 2rid session of 10 rain duration, separated from the first by an interval which varied with the group, from 0 min to 24 hr. The performances were thus measured after 7 different intervals: 0 min, 5 min, 1 hr, 3 hr, 6 hr, 12 hr, and 24 hr. There were 10 mice in each group except for the 12-hr group which had only 9. At the beginning of the 1st session, the animals presented a weight loss of 18 to 20%. Between the 1st and 2nd sessions, 30 min after the 1st session, the animals of the different groups were given a quantity of food proportional to the interval duration. For the 0 min, 5 min, 1 hr, 3 hr, and 24 hr groups, we counter-balanced the effects of the time and day of the sessions between the groups, as previously. The animals of the 6-hr group all

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underwent the 1st session in the morning and the 2nd session in the afternoon; for the animals of the 12-hr group, 5 subjects underwent the 1st session in the morning, and 4 subjects in the afternoon. Results First session. The random assignment of the animals into the different groups is satisfactory. An analysis of variance for the discrimination ratio recorded during the two successive 10-min blocks shows the homogeneity of the performances [F= 0.61 (lst block); F = 0.53 (2nd block); dr= 6/62]. Second session. An analysis of variance carried out at the 2nd session shows a highly significant effect of the interval on the discrimination ratio ( F = 13.84; df=6/62; P < 0 . 0 0 1 ) . The curve in Fig. I sets out the performance level in function of the interval. One notes that the performances of the 0-min, 5-min, and 1-hr groups are statistically indistinguishable. On the other hand, one notes a significant increase in performance between 1 and 3 hr; this increase continues for the 6- and 12-hr intervals, and becomes statistically indistinguishable between 12 and 24 hr. The discrimination ratio is probably the clearest single measurement for performance appreciation, but performance cannot be correctly interpreted without taking t h e separate SD and S A response rates into consideration (Leaton & Kreindler, 1971).

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3hr 6hr 12'hr 24hr INTERVALBETWEENTHE 1st and 2nd SESSIONS (Log Scale)

Fig. 1. Discrimination ratio (M -+SEM) during the first 10-min block of the second session as a function of the interval between the first and second sessions. The arrow indicates the mean ratio for the 7 pooled groups during the second 10-min block of the first session. * P < 0.05, 3 hr vs. 1 hr; **P< 0.01, 6 hr vs. 1 hr; ***P< 0.001, 12 hr and 24 hr vs. 1 hr.

IMPROVEMENT OF PERFORMANCE WITH TIME

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Fig. 2. Mean gains (positive numbers) and mean losses (negative numbers) in response to SD and S A between the first 10-min block of the second session and the second 10-min block of the first session as a function of the interval between sessions. As shown in Fig. 2, the improvement of the discrimination ratio results from: 1. The increase in the number of responses to SD. This increase is function of the interval. It is, however, extremely rapid, and statistically distinguishable between the 0- and 5-min intervals ( t = 2 . 9 4 , d f = 1 8 ; 0.01 > P > 0 . 0 0 1 ) . It reaches an asymptotic level as fro m 1 hr (the responses to SD from 1 to 24 hr are not statistically distinct). 2. The decrease in the number of responses to S A. This decrease is function of the interval. This process is considerably slower than the first one. O n e n o t e s , indeed, that the worst performances are recorded for the 1-hr interval, and that the mean of the responses to S a progressively decreases from 1 to 12 hr (31-+2 responses, and 13.4+ 1.8 responses, respectively), whilst the responses to SD are asymptotic. Thus, if one compares the mean o f the number of responses to S A for the 1-hr group to those of the following groups, one notices a significant difference with the 6-hr (t = 3.17; df = 18; P < 0.01), 12-hr (t = 6.25; dr= 17; P < 0.001) and 24-hr ( t = 4.63; dr= 18; P < 0 . 0 0 1 ) groups. The comparison with the 3-hr group does not reach the level of statistical significance (t = 2.05; df= 18; 0 . i 0 > P > 0.05). DISCUSSION Briefly, our results show that a 24-hr interval significantly improves performance in appetitive operant conditioning, whether it be either under a

98

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continuous reinforcement schedule or on discriminative operant conditioning. This improvement is time-dependent: It is not distinguishable before 3 hr and is maximal after 12 hr. Certain authors, notably Kamin (1957), have demonstrated variations in performance levels in function of the interval between two learning sessions (retention interval). These experiments reveal a temporary drop in performance which can occur very early (Riege & Cherkin, 1971) or later (from 1 to 8 hr, in Halloway & Wansley, 1973). Only the decrease in performance on the responses to S A, observed for the t-hr interval (Fig. 2) can be compared to the Kamin effect; this decrease, however, is not significant in relation to the 0- and 5-rain intervals. Contrary to previous results, our results demonstrate a performance g.ain in relation to a zero retention interval. There are relatively few similar results in the literature (Bunch & Magdsick, 1933; quoted by Munn, 1950; Anderson, 1940; Deutsch, 1973). From this, it seems to us that a certain number of hypotheses put forward to explain the disparities observed in retention levels (Denny & Ditchman, 1962; Halloway & Wansley, 1973), must be excluded, and it seems plausible to us to put forward the hypothesis that the gain observed could be the expression of a memory process. In the first place, this gain would appear to exist only for partial learning and would appear to be function of the level of the original learning: It would appear to be greater for average information levels than for excessively low or excessively high levels (experiments 1 and 2). In the second place, the establishment of this gain would appear to be progressive, and occur, distinguishably, between 3 and 12hr after the original learning. Although these delays are compatible with the delays necessary for the establishment of a long-duration memory (Halstead & Rucker, 1970), it appears premature to us at present to accord too great an importance to the values reported here. Thus, the gain observed by Bunch and Magdsick (1933) in the learning of a water maze in the rat, occurs uniquely between 0 rain and 1 hr, whereas it stretches between I min and 24 hr in a passive avoidance learning in the mouse, C57/B16 (Randt et al., 1971). It is likely, therefore, that the animal and the behavior used, together with the level of the partial learning, are the source of numerous fluctuations in these values, without considering, nonetheless, that the results of Huppert and Deutsch (1969), showing a performance improvement between 7 and 10 days, fall within this framework. For these reasons, only the qualitative aspect of the phenomenon deserves to be taken into consideration. Its evolution recalls the consolidation phase. The consolidation phase, however, is not considered as being gaininducive, but as the simple fixation of a performance level reached on the zero retention interval. Certain authors (Irwin et al., 1968; Bloch, 1970) have insisted on the elaborative and dynamic character of this phase; our results

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support this concept, and seem to show that the information received by the central nervous system is treated, at least in the case of the incomplete learning. At present, it is difficult to say what this treatment consists of. Nonetheless, two remarks can be made: In the 3rd experiment, the improvement in performance on the positive responses (SD) is small and rapid (Fig. 2); on the other hand, the improvement of the negative responses (S A) begins only after 3 hr, and it is this improvement which is, in fact, responsible for the overall improvement in performance (Fig. 1). Thus, the treatment imposed by the central nervous system appears to concern essentially the inhibition of a previously acquired response that has become useless. In the 1st experiment, the inhibitory processes appear less important, as the animal is placed in a situation of continuous reinforcement. Nonetheless, in this situation of incomplete learning, the behavior of the animal remains nonselective, and burdened with redundant behaviors, moreover distinguishable by simple observation. In this case, the treatment imposed by the central nervous system would appear to be a selective operation inducing a highly adapted behavior 24hr afterwards. Such a hypothesis implies the bringing into play of inhibitory operations inducing the elimination of useless information and inadapted behavior. The performance improvement in our three experiments would appear to result from the bringing into play of selective inhibitory operations. On the plane of the nervous structure concerned, one is justified in thinking that the hippocampus plays a role in this improvement. Destrade et al. (1973) test the effect of subconvulsive bilateral stimulation of the hippocampus after a very incomplete appetitive operant learning; 24 hr afterwards, the performance level of the nonstimulated control mice is identical to the level at the end of the original learning. On the other hand, the stimulated mice reveal a very considerable improvement in their performance. Hippocampal stimulation, therefore, has created an improvement comparable to that which we observe here in natural conditions after longer partial learning. Nonetheless, it is important to discover whether the evolution with time of the artificially created gain is comparable to that which has been demonstrated in natural conditions. REFERENCES Anderson, A. C. (1940). Evidence of reminiscence in the rat in maze learning. J. Comp. Psychol. 30, 399-412. Bloch, V. (1970). Facts and hypothesis concerning memory consolidation process. Brain Res. 24, 561-575. Denny, M. R., & Ditchman, R. W. (1962). The locus of maximal "Kamin effect" in rats. J. Comp. PhysioL Psychol. 55, 1069-1070.

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Destrade, C., Soumireu-Mourat, B., & Cardo, B. (1973). Effects of posttrial hippocampal stimulation on acquisition of operant behavior in the mouse. Behav. BioL 8, 713 -724. Deutsch, J. A. (1973). The cholingeric synapse and the site of memory. In J. A. Deutsch (Ed.), "The Physiological Basis of Memory," New York: Academic Press, pp. 59-78. Gabriel, M. (1968). Effects of intersession delay and training level of avoidance extinction and intertrial behavior. J. Comp. Physiol. PsychoL 66,412-416. Gabriel, M. (1970). Intersession exposure of rabbits to conditioning apparatus, avoidance extinction and intertrial behavior. J. Comp. Physiol. Psychol. 72, 244-249. Geller, A., Jarvik, M. E., & Robustelli, F. (1970). Incubation and the Kamin effect. J. Cornp. Physiol. Psychol. 85, 61-65. Halloway, F. A., & Wansley, R. (1973). Multiphasic retention deficits at periodic intervals after passive avoidance learning. Science 180, 208-210. Halstead, W. C., & Rucker, W. B. (1970). The molecular biology of memory. In W. L. Byrne (Ed.), "Molecular Approaches to Learning and Memory," New-York: Academic Press, pp. 1-14. Huppert, F. A., & Deutsch, J. A. (1969). Improvement in memory with time. Quart. J. Exper. Psychol. 21,267-271. Irwin, S., Banuazizi, A., Kalsner, S., & Curtis, A. (1968). One trial learning in the mouse. I. Its charactersitics and modification by experimental seasonal variables. Psychopharrnacologia 12, 286-302. Jaffard, R., & Cardo, B. (1970). Influence of intracortical injections of ribonuclease on the acquisition and retention of operant behavior and visual discrimination. Phsyiol. Behav. 5, 1303-1308. Jarvik, M. E. (1972). Effects of chemical and physical treatments on learning and memory. Annu. Rev. Psychol. 23,457-486. Kamin, L. J. (1957). The retention of an incompletely learned avoidance response. J. Comp. Physiol. Psychol. 50,457-460. Kamin, L. J. (1963). Retention of an incompletely learned avoidance response: some further analysis. J. Cornp. Physiol. Psychol. 56, 713-718, Leaton, D. E., & Kreindler, W. R. (1971). Effects of physostigmine and scopolamine on operant brightness discrimination in the rat. Physiol. Behav. 99, 121-123. Munn, N. L. (1950). "Handbook of Psychological Research on the Rat," Houghton Mifflin Company, The Riverside Press, Cambridge, Mass. Randt, C. T., Barnett, B. M., McEven, B. S., & Quartermain, D. (1971). Amnesic effects of cycloheximide on two strains of mice with different memory characteristics. Exp. Neurol. 30, 467-474. Riege, W. H., & Cherkin, A. (1971). One-trial learning and biphasic time course of performance in the goldfish. Science 172, 966-968. Soumireu-Mourat, B., & Cardo, B. (1972). Hypothermie profonde chez la Souris: perturbations de l'activitd dlectrique centrale et d'un apprentissage d'approche. Physiol Behav. 9, 183-190.