Short-term memory impairment following chronic alcohol consumption in rats

Neuro~ycholopia, Vol. 16, p. 545 to SS3. @ Pcrgamoa Prms Ltd. 197i. Printed in Groat Britab.

SHORT-TERM MEMORY IMPAIRMENT FOLLOWING CHRONIC ALCOHOL CONSUMPTION IN RATS DON W. WALKERand BRUCE E. HUNTER Veterans Administration Hospital and Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 32610, U.S.A. (Received 3 May 1978) Abstract-Prolonged alcohol consumption (20 weeks), concomitant with adequate nutrition, was found to result in a residual short-term memory deficit after a 2-month alcohol-free period. Alcohol was administered in a liquid diet containing 35-37x ethanol-derived calories. One control group was pair-fed the same diet, except that sucrose was isocalorically substituted for ethanol. A second control group received pelleted laboratory food. After a aday alcoholfree period, short-term memory was assessed by training the rats on a discrete-trial temporalalternation task in which bar presses were reinforced on alternate trials. Performance of the alternation problem was evaluated under conditions of short (20 set) and long (50 set) between-trial retention intervals. Although alcohol-treated-rats were relatively unimpaired when the retention interval was short, they were severely impaired with the long retention interval. In addition, the performance of alcohol-treated rats was severely disrupted when a distractor task was introduced during the short retention interval. The results were discussed relative to the similar short-term memory impairments of chronic alcoholic and alcoholic Korsakoff patients. BRAIN damage resulting in impairment of learning and memory often observed in chronic alcoholism [l-3] has been traditionally considered to result from malnutrition, especially thiamine deficiency [4]. However, brain damage and associated mental deterioration have been reported in alcoholic patients with no history or clinical evidence of malnutrition, head trauma or exposure to other toxic agents [5-g]. It appears likely, then, that chronic alcohol consumptionper se can produce brain damage despite adequate nutrition. However, proper control over genetic, environmental and nutritional variables is difficult or impossible using alcoholic patients. Animal investigations can therefore make valuable contributions toward the determination of the nature and characteristics of the potential neurotoxicity of ethanol. Using a nutritionally controlled rodent model of chronic ethanol exposure, we have demonstrated that 3-7 months of ethanol consumption results in the subsequent impairment of shuttle-box avoidance acquisition [9, lo], and timing behavior [II]. Ethanol was administered in these studies by its incorporation into a nutritionally adequate liquid diet. Control groups received pelleted laboratory food or were pair-fed with the ethanolconsuming animals by isocaloric substitution of sucrose for ethanol in the diet. The ethanolinduced impairment in acquisition remains unabated even after an ethanol-free period of 18 weeks [9]. Recently, other laboratories have confirmed our reports of residual alcoholinduced deficits in shock avoidance [12] and maze learning [13, 141. It seems well established, then, that prolonged alcohol exposure per se, without malnutrition, can result in residual learning deficits in mice and rats. However, it is not yet known whether prolonged 545

546

DON W. WALKERand BRUCE E. HUNTER

ethanol exposure per se will also produce an impairment of short-term memory in animals. The present experiment was designed to test the hypothesis that prolonged alcohol consumption in rats would result in an impairment of memory processes similar to that seen in chronic alcoholic patients [15-191. In order to test this hypothesis, rats previously exposed to alcohol, and their controls, were trained in a temporal single-alternation task which we have previously used to examine the memory processes of rats with lesions of the hippocampus [20, 211. Since no external cue is available in this task, an increase in the intertrial interval (ITI) lengthens the time that the animals must remember the consequences of the previous trial in order to perform appropriately on the following trial. Accordingly, rats with a history of prolonged alcohol consumption and their controls were trained on the temporal alternation problem to criterion performance under conditions of both a short and long IT1 (retential interval). Susceptibility to interference was also examined by interpolating a distractor task during the short retention interval. METHOD Animals The animals were 24 male Long-Evans hooded rats purchased from Charles River. The rats were approx 75 days old and weighed 175-200 g at the beginning of the experiment. They were individually housed in stainless steel cages in a colony room with an automatic 7:OO a.m. to 7:00 p.m. light cycle. Apparatus All behavioral testing was done in three identical Lehigh Valley operant chambers and cubicles (No. 1417) programmed by Grason-Stadler series 1200 logic modules. Each operant chamber was equipped with two retractable levers on one end. The delivery port of a food magazine was centered between the two levers. Associated with each chamber was a pellet feeder that delivered 45 mg food pellets. Procedure Bar-press training. All rats were reduced to 80% of their free-feeding body weights and trained to barpress for 45 mg food pellets (P. J. Noyes Co.) on a continuous reinforcement schedule (CRF). Each rat was given daily 15 min. CRF sessions until a response rate of 75 or more responses per session was obtained (5-8 sessions). After CRF training was completed, all rats received water and pelleted laboratory food (Ralston Purina Laboratory Chow) without restriction for 2 weeks to allow them to reattain their original weights before the experimental diets were begun. Alcohol administration. Following the 2-week refeeding period, the rats were weighed and divided into three equal groups matched for weight. The experimental group was given an ethanol-containing liquid diet (group A). One control group received a sucrose-containing liquid diet (group S) and a second control group received laboratory chow and water (group LC). The composition and nutritional adequacy of the liquid diets has been reported in detail previously [lo]. Briefly, the alcoholcontaining liquid diet contained 35-37 % ethanol-derived calories (8.1-8.7x v/v ethanol) and was prepared by mixing a 63.3 % v/v stock solution of ethanol with Metrecal Shape (Mead Johnson; no longer available). The sucrosecontaining diet was prepared in the same manner except sucrose was isocalorically substituted for ethanol. Both the ethanol and sucrose diet were additionally fort&d with Vitamin Diet Fortification Mixture, 0.3 g/100 ml, and Salt Mixture XIV, 0.5 g/100 ml (both from Nutritional Biochemicals Corporation). The liquid diets provided 1.3 Kcal/ml. All liquid diets were prepared fresh daily and administered in calibrated bottles through stainless steel drinking tubes with openings enlarged to 4.0 mm. The rats were maintained on their respective diets for 20 weeks. Group S rats were individually pairfed with group A rats so that they received identical calories and nutrients during the entire 20-week period. Consumption of the liquid diets was measured daily and ethanol consumption was calculated as g per kg per day.-The rats were weighed weekly throughout the 20-week period-of diet administration. For the first 10 weeks the liquid diets contained 35 “/. ethanol (8.1% v/v ethanol) or sucrose-derived calories. After 10 weeks, the per cent ethanol or sucrose:derived&oried was increased to 37% (8.7% v/v ethanol) for the remainder of the 20-week period of diet administration. This increase in ethanol concentration was initiated in order to offset partially the slight decrease in ethanol consumption (in g/kg) as body weights increased. Following this 20-week experimental diet period, all rats were placed on pelleted laboratory food and water without restriction for a period of 2 months before behavioral testing was begun. Behavioral testing. After 2 months of unrestricted access to laboratory food and water, all rats were reduced

CHRONTC

ALCOHOL

co NSUMPTION

IN

RATS

547

body weights and maintained at that weight by restricted feeding throughout the remainder of the experiment. One week after each rat had been reduced to 85% of its free-feeding weight,each rat received a 15 min. CRF session daily for 5 days. After 5 days of CRF retraining, all rats

to 85 % of their fmfeeding

were pressing at a rate of at least 100 responses per session indicating that they retained the response acquired several months previously. There were no group diierences in rate of response on the CRF schedule. Training on a single-alternation go, no-go task was initiated on the day following completion of the CRF retraining. Each session consisted of 20 discrete trials per day. Each trial consisted of a 20 set presentation of the retractable lever on the right of the chamber followed by an inter-trial interval (ITI) during which the lever was retracted (unavailable). On odd-numbered trials the rats were reinforced (one 45 mg food pellet) for each response. On even-numbered trials responses were not reinforced. No external cues were given. The dependent variables were the latency (in seconds) to the first response and the number of responses on each trial. A well-trained rat on this task makes few responses on the no-go trials and responds with a short latency on go trials and a long latency (or no response at all) on the no-go trials [20,21]. Since no external cues are available, the rat must presumably remember the consequences of the previous trial in order to respond appropriately on the subsequent trial. The absolute latencies and the number of responses were converted to latency and response ratios for each animal for each session. The latency ratio for each animal is the mean latency to the first response on go trials/the mean latency to the lirst response on no-go trials for each session of 20 trials. The response ratio for each animal is the mean number of responses on no-go trials/mean number of responses on go trials for each session. Latency and response ratios of less than 1.OOindicate a longer latency to respond and fewer responses on the non-reinforced no-go trials. Thus, the smaller the latency and response ratios, the better the performance on the alternation pattern. The ITI (retention interval) at the beginning of temporal alternation training was 20 set for all rats. When a rat reached a criterion of five successive sessions with both latency and response ratios less than 0.25, or if criterion performance was not reached in 30 sessions (600 trials), the retention interval was increased to 50 sec. The first session of the string of five sessions in which criterion performance was achieved was considered the criterion session. When the same criterion performance was attained at the 50 set retention interval. or criterion was not attained within 50 sessions (1000 trials), the retention interval was changed back to 20 sec. The animals were retested at the 20 set retention interval to verify that any performance decrement at the 50 set interval was indeed a result of the increased retention duration required and not due to extraneous variables. In addition, after each rat reattained criterion performance at the 20 set interval, the susceptibility to interference was examined by interpolating a distractor task during the ITI while the alternation problem continued. The interpolated distractor task consisted of the presentation of the left lever during the ITI of the alternation problem which continued on the right lever. Thus, during the retention interval of the alternation problem, the left lever was made available for the middle 10 set of the 20 set ITI on a CRF schedule. The interpolated distractor task was continued until each rat again reached criterion performance on the alternation problem or for a maximum of ten sessions (200 trials).

RESULTS Alcohol administration During the 20-week period of alcohol administration the overall mean consumption of ethanol was 11.7 g per kg per day for group A rats. The ethanol consumption slowly declined from 13-9 g per kg per day during the first four week period to 101 g per kg per day during the last 4 weeks. This slowly declining level of ethanol consumption is typical during prolonged exposure [lo, 111, and is a result of increasing body weight without a concomitant increase in total caloric intake. The three groups gained body weight at an equal rate throughout the 20-week period of experimental diet administration. At the beginning of the diet administration period the mean (& S.E.) body weights were 261 g (&- 8.3) for the alcohol group, 264 g (& 6.5) for the sucrose group and 262 g (* 4.7) for the lab chow group. At the end of the 20week period of diet administration the mean (-& S.E.) weights were 504 g (& 13.0) for the alcohol group, 498 g (&- 10-8) for the pair-fed sucrose group and 507 g (&- 20-O) for the lab chow group. Behavioral testing Although group A was unimpaired in performance

of the temporal alternation

task

DON W. WALKER and BRUCE E. HUMER

548

when the retention interval was 20 set, they were strikingly impaired when the retention interval was increased to 50 sec. In addition, the interpolation of a distractor task during the retention interval markedly disrupted the performance of group A on the alternation task even when the retention interval was only 20 sec. The number of sessions required to reach criterion performance for each rat under Table 1. Number of sessions to criterion for each rat under each experimental Experimental Rat No.

20 set ITI

condition

SOsecITl

20 set IT1 Retest

Alcohol group 5Of 50t 50t

1A 2A 3A

::t 30t

4A 5A 6A 7A 8A Mdn

11 19 10 12 13 16.00

1s

20

2s :: 5s 6s 7s 8s Mdn

11 13 9 15 10 17 11 12.00

condition

42 20 21 50t &O*

: 6

10t 1OP 2

;

l&

3 2 3.00

1dt 2 9.50+*

Sucrose control group 8 2 8” ; 17 10 &I

20 set IT1 Interpolated Task

8

5 42

: 7

22 1 6 2.00

; 4

21 :

: 1 2 1 6 3 3.00

:.OO

Lab chow control group :; 3L 4L 5L 6L 7L 8L Mdn

13 27 12 1: 20 11 10 11.50

222 7 11 6 8 21 8 8.00

1 2 l.00

Note: Criterion performance was defined as five consecutive sessions in which both latency and response ratios were less than 0.25. *Significantly different (P < 0.001) from both control groups (Mann-Whitney two-tailed test). **Significantly different (P < 0.05) from both control groups (Mann-Whitney two tailed test). tFailed to reach criterion performance within preset limit of 30 sessions (20 set-ITI) or 50 sessions (50 set-ITI). -Died of unknown cause before testing completed.

each of the four successive phases of behavioral testing is presented in Table 1. The number of sessions to criterion performance for the three groups under each of the four experimental conditions was compared with a Kruskal-Wallis one-way analysis of variance by ranks. Mann-Whitney tests (two-tailed) were used for group comparisons following a

CHRONIC ALCOHOL co-

549

NMRATS

significant Kruskal-Wallis test. These non-parametric analyses were used because some rats failed to reach criterion and thus an artificial ceiling was imposed on the data. There were no significant differences in sessions to criterion among the three groups under the 20 set retention interval condition. However, when the retention interval was increased to 50 set, group A required considerably more sessions to reach criterion performance than either group S or Group LC (both P < 0.001). In fact, half of the rats in group A were unable to reach criterion in the preset 50 session (1000 trials) limit. Note, however (see Table l), that all group A rats were able to reattain criterion performance without deficit when retested under the 20 set IT1 condition. When all rats were performing at criterion under the 20 set retention interval, the distractor task was introduced during the ITI. The introduction of the distractor task disrupted the performance of all groups initially, but especially that of group A. As can be seen in Table 1, group A took significantly more sessions to reattain criterion performance than either control group (P < 0.05). In fact, again half of group A rats were unable to reach criterion performance within the preset limit of 10 sessions. There were no statistically significant differences between the two control groups under any of the experimental conditions. Although the sessions-to-criterion data presented in Table 1 appear straightforward and clear, this table does drastically abridge the total amount of data collected. For this reason, a summary of the absolute latency and response data under each experimental condition is presented in Table 2. Table 2 gives the mean latencies in seconds to the first response and Table 2. Mean latencies* in seconds, mean number of responses and mean latency and response ratios on the first and criterion sessions under each experimental condition 20 set ITI

Experimental condition 5OsecITI

Group First Go latency

No-go latency Latency ratio No-go responses Go responses Response ratio Go latency No-go latency Latency ratio No-go responses Go responses Response ratio Go latency NO-ROlatency

Late&y ratio No-go responses Go responses Response ratio

8.36 7.13 1.17 78.0 42.5 2.06

Criterion session 1% 0:17 9.38 75.00 0.16

8.15 1.11 62.10 33.30 2.15

2.11 16.42 0.13 6.50 67.50 0.10

7.76 6.98 1.21 77.63 41.63 2.00

2.61 16.38 0.16 6.88 79.63 0.09

8.54

First Criterion session session Alcohol 2.69 3.08 3.65 11.25 0.76 0.29 37.00 13.50 66.90 60.60 0.55 0.24 Sucrose 3.78 2.08 5.85 16.27 0.72 0.13 35.00 4.00 56.30 55.30 0.67 0.07 Lab chow 3.83 2.18 6.44 15.38 0.14 0.61 28.30 5.90 60.00 74.30 0.56 0.08

20 set IT1 Retest First Criterion session 2.81 11.27 0.26 14.80 63.10 0.24

1.93 15.36 0.13

2OsecITI Interpolated task First Criterion

7K 0:12

3.97 8.51 0.52 27.30 64.40 0.43

2.65 11.24 0.26 11.10 64.30 0.19

2.28 16.65 0.14 4.63 54.13 0.09

2.17 17.66 0.12 2.50 64.75 0.04

3.68 15.00 0.24 7.50 51.13 0.17

2.42 18.20 0.14 2.40 54.50 0.04

2.26 17.38 0.13 3.60 82.70 0.05

2.05 18.40 0.11 3.14 76.70 0.03

3.24 15.20 0.23 7% 0.12

1% 0:14 3.70 74.10 0.06

Note: If a rat failed to reach criterion under any condition then the data for the last session under that experimental condition was used to calculate the means for the criterion session column; otherwise the data from the tirst of a string of five criterion sessions was used. *The maximum latency to the first response on an individual trial is 20 sec.

550

DON W. WALKERand BRUCEE. ‘Hmmt

mean number of responses on go (reinforced) and no-go (nonreinforced) trials under each experimental condition. These data are given for the first session and the criterion session (last session if rat failed to reach criterion) for each experimental condition. Table 2 also presents the mean group latency and response ratios calculated from the mean ratios for individual rats for each session. One way analyses of variance (ANOVA) followed by Newman-Keuls group comparisons were used to test for group differences in latency and response ratios under the different experimental conditions. No differences among the latency or response ratios of the three groups were detected under the initial 20 set retention interval either on the first or criterion sessions. It can be seen from Table 1 that all groups were performing well on the criterion session. Few responses were being made on no-go trials and latencies were short on gotrials and long on no-go trials, indicating mastery of the alternation problem. As Table 2 indicates, the performance of all groups was equally disrupted initially by the shift to a 50 set retention interval. Recall, however, that the control groups required many fewer sessions to reach criterion performance than did group A under the 50 set retention interval condition (Table 1). Group A also had significantly higher (P < 0.01) latency and response ratios at the end of training at 50 set IT1 than either control group (Table 2) corroborating the trials-to-criterion data. Recall that following training under the 50 set IT1 condition the IT1 was shifted back to 20 set to reestablish criterion performance in all rats prior to introducing the interpolated distractor task. A one-way ANOVA revealed no statistically significant differences among the groups in latency or response ratios on the criterion session of the 20 set IT1 condition (Table 2). The introduction of the distractor task severely disrupted the performance of group A rats on the alternation problem, while only mildly influencing the control groups (see Table 2). Both latency and response ratios of group A were significantly (P < 0.01) higher than either control group on the first session in which the distractor task was introduced. Moreover, both latency and response ratios of group A were still significantly (P < 0.01) higher than those of either control group on the criterion session under conditions of the interpolated distractor task. In summary, the performance of group A was severely disrupted by increasing the retention interval from 20 to 50 set, and by the introduction of a distractor task interpolated during the 20 set retention interval. These conclusions were supported by analysis of both trials-to-criterion data and raw latency and response data. DISCUSSION It is clear from the present results that prolonged alcohol consumption resultsin a marked impairment in short-term memory processes in the rat. This short-term memory deficit is particularly evident when the retention interval is increased or when a distractor task is introduced during the retention interval. Presumably when the retention interval is increased there is more opportunity for the occurrence of competing responses or irrelevant stimuli to occur and disrupt the memory trace. It appears, then, that the memory traces of rats previously exposed to alcohol are more susceptible to disruption either by experimenter-induced or naturally occurring irrelevant stimuli. The short-term memory impairment of rats previously exposed to alcohol reported here is strikingly similar to the memory impairment of chronic alcoholic and alcoholic Korsakoff patients [15,22] and patients with bilateral hippocampal damage [23,24]. Chronic alcoholic

CHRONIC

ALCOHOL CONSUMPTION

IN

RATS

551

and alcoholic Korsakoff patients [15], and patients with hippocampal damage [251 are particularly sensitive to increases in retention intervals and interference from distractor activities during short-term memory tasks. Additionally, lesions of the hippocampus in rats result in a short-term memory deficit virtually identical to that observed in the present experiment. Rats with hippocampal lesions were trained on the same alternation problem used in the present experiment and were also impaired in performance when the retention interval was increased [21], or a distractor task was introduced during the retention interval

WI* The similarity in the characteristics of the short-term memory deficits observed among chronic alcoholic and alcoholic Korsakoff patients [15, 221, rats chronically exposed to alcohol (this study) and patients [23, 251 and rats [20, 211 with lesions of the hippocampus suggest the possibility of a common site of brain damage in these populations. Based on neuropathological studies of alcoholic Korsakoff patients, VICTORet al. [3] have suggested that damage to the dorsomedial thalamus is consistently correlated with impaired memory while BRION [26] has placed more importance on the mammillary bodies. It is possible, however, that lesions of the dorsomedial thalamus and mammillary bodies in alcoholic Korsakoff patients are the result of malnutrition as previously suggested [3, 43 and not a result of alcohol per se. However, nutritionally controlled animal studies have demonstrated that prolonged alcohol consumption per se results in learning and memory impairment similar to that seen in alcoholic patients presumably reflecting similar underlying neuropathology [9-11, 13, this study]. Accordingly, it is of considerable interest to determine if prolonged alcohol consumption in animals, under nutritionally controlled conditions similar to the present experiment, results in identifiable neuropathology. We have recently conducted such an experiment in our laboratory and have observed a substantial alteration in dendritic morphology in the hippocampal complex of mice following four months of alcohol consumption [26]. Quantitative and qualitative Golgi methods were used to examine the brains of mice that received alcohol-containing or control diets for 4 months followed by a 2-month alcohol-free period. Chronic alcohol consumption resulted in a substantial loss (approx 50%) of dendritic spines on hippocampal pyramidal cells and dentate gyrus granule cells compared to control mice. In addition, qualitative analysis revealed a substantial attenuation of pyramidal cell dendrites. No quantitative or qualitative alterations were observed in dorsomedial thalamus. Although other brain regions must yet be examined, the results keep open the possibility that residual learning and memory impairments in chronic alcoholics and alcohol-consuming animals may be related to damage of the hippocampus. Future research in which both quantitative behavioral and neuropathological data are collected in the same animals following prolonged alcohol consumption should aid in determining the nature of the neuropathology underlying the learning and memory deficit in alcoholic patients. Although caution is necessary when generalizing from animal studies to the human condition, it is clear that the proper controls necessary in studies of this sort can be attained in animal studies. The previous findings that prolonged alcohol consumption concomitant with adequate nutrition, results in anterograde deficits in acquisition of a variety of behavioral tasks [9-l 1, 131, but does not disrupt retention of a remotely learned response [27], together with the results of the present experiment, indicate that nutritionally controlled animal experiments will be useful in defining the neurotoxic effects of alcohol in humans.

552

DON W. WALKER and BRUCP.E. HUNTER

Acknowledgements-This research was supported by the Veterans Administration and by the National Institute on Alcohol Abuse and Alcoholism rNIAAA1. grant No. AA-00200 to D.W.W. B.E.H. was suuported by NIAAA predoctoral fellowship no. AA05022:‘We thank PAT BURNETT,LARRYEZELLand DOROT& ROBINSONfor expert technical assistance.

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Press, Los Angeles, 1966. TALLAND,G. A. Deranged Memory. Academic Press, New York, 1965. VICTOR, M., ADAMS, R. D. and COLLINS, G. H. The Wernicke-Korsakofl Syndrome. F. A. Davis, Philadelphia, 1971. VICTOR,M. and ADAMS,R. D. On the etiology of the alcoholic neurologic diseases with special reference to the role of nutrition. Am. J. Nutr. 9, 379-397. 1961. BREWER, C. and PERRET~, L. Brain damage due to alcohol consumption; an air-encephalographic, psychometric, and electroencephalographic study. Br. J. Addic. 66, 170-182, 1971. HAUG, J. 0. Pneumoencephalographic evidence of brain damage in chronic alcoholics. Acta Psychiat. Stand., S&p!: 203,135-143, 1968. JONES,B. and PARSONS,0. A. Impaired ability in chronic alcoholics. Archs Gen. Psychiat. 24, 71-75, 1971. SMITH,J. W., BURT, D. W. and CHAPMAN,R. F. Intelligence and brain damage in alcoholics: a study of patients of middle and upper social class. Qt. J. Stud. Afcohol34,414422, 1973. FREUND,G. and WALKER,D. W. Impairment of avoidance learning by prolonged ethanol consumption in mice. J. Pharmacol. Exp. Ther. 179,284292, 1971. WALKER, D. W. and FREUND, G. Impairment of shuttle box avoidance learning following prolonged alcohol consumntion in rats. Phvsiol. Behav. 7. 773-778.1971. WALKER, D. W: and FREUND, G. Impairment of timing behavior following prolonged alcohol consumption in rats. Science, N. Y. 182, 597-599, 1973. _ SOTZING,J. H. and BROWN,T. S. Chronic intermittent ethyl alcohol inhalation and avoidance learning. Pharmacol. Biochem. Behav. 5,417-421, 1976. BOND, N. W. and DIG~STO, E. L. Impairment of Hebb-Williams maze performance following prolonaed alcohol consumotion in rats. Pharmacol. Biochem. Behav. 5.85-86. 1976. FEAR, K. A., KALANT,H. and LEBLANC,A. E. Residual learning def&it after heavy exposure to cannabis or alcohol in rats. Science, N.Y. 193, 1249-1251, 1976. BUITERS, N., CERMAK,L. S., MONTGOMERY, K. and AD~NOLF~,A. Some comparisons of the memory and visuoperceptive deficits of chronic alcoholics and patients with Korsakolf’s disease. Alcoholism Clin. Exp. Res. I, 73-80, 1977. CERMAK,L. S. and Bw~-~ERs,N. The role of interference and encoding in the short-term memory deficits of Korsakoff patients. Neuropsychologia 10,89-95, 1972. CERMAK,L. S., BUTIXRS, N. and G~~DGLA~.~,H. The extent of memory loss in Korsakoff patients. Neuropsychologia 9, 307-315, 1971. DELUCA, D., CERMAK,L. S. and BUTTERS,N. An analysis of Korsakoff patients’ recall following varying types of distractor activity. Neuropsychologia 13,271-279, 1975. BADDELEY,A. D. and WARRINGTON,E. K. Amnesia and the distinction between long and short-term memory. J. verb. Learn. verb. Behav. 9, 143-148, 1970. WALKER, D. W. and MEANS, L. W. Single-alternation performance in rats with hippocampal lesions: Disruption by an irrelevant task interposed during the intertrial interval. Behav. Biol. 9, 93-104, 1973. WALKER, D. W., MESSER,L. G., FREUND, G. and MEANS, L. W. Effect of hippocampal lesions and intertrial interval on single-alternation performance in the rat. J. camp. physioi. Psychol80, 469477, 1972. Burrsas, N. and CERMAK, L. Some analyses of amnesic syndromes in brain-damaged patients. In The Hippocampus, Vol. 2: Nemophysiology and Behavior, R. L. ISAACsoNand K. H. PRIBRAM(Editors). pp. 377409. Plenum Press, New York, 1975. MILNER, B. The memory deficit in bilateral hippocampal lesions. Psychiat. Res. Rep. 11, 43-52, 1959. MILNER, B., CORKIN, S. and TEUBER,H. L. Further analysis of the hippocampal amnestic syndrome. Neuropsychologia 6, 267-282, 1968. SIDMAN,M., S~~DDARD, L. T. and MOHR, J. P. Some additional quantitative observations of immediate memory in a patient with bilateral hippocampal lesions. Neuropsychologia 6, 245-254, 1968. RILEY, J. N. and WALKER, D. W. Morphological alterations in hippocampus following chronic alcohol consumption in mice. Science, In press. WALKER,D. W. and HUNTER, B. E. Prolonged alcohol consumption in the rat: absence of retrograde amnesia for an avoidance response. Pharmacol. Biochem. Behav. 2,63-66, 1974.

553 Rbsum& : On a constat avec une nourriture

que la prise prolongSa d'alcool

(20 semaines)

adequate entrainait un deficit dans la m&moire 5

court terme rssiduelle apr&s une periode de 2 mois libre d'alcool. L'alcool etait administre aux rats dans le regime liquide contenant 35-37% de calories d&ivfes

de l'dthanol. Un.groupe contrble recevait

la aSme regime mais du saccharose &ait calorique a 1'0thanol.

substitue pour la time valeur

Un secondgroupecontr8ierecevait de la nourri-

ture sous forme de boulettes. Ap r6 s une pdriode libre d'alcool de 60 jours, on etudiait la memoire a court terme en entrainant les rats sur une Bpreuve d'alternance

temporelle a essais isol&

dans 1esquel.s cha-

que pression du levier etait renforcee sur les essais altern&. performances

sur les probl&nes d'alternance

conditions d'intervalles

Les

Btait Bvaluees sous des

de retention entre les essais,

courts

(20 se-

condes) et longs (50 secondes). Bien que les rats traites a l'alcool ne presentaient relativement pas de ddficit avec un fntervalle de rdtention court, 11s Btaient gravement deficitaires prolong6. En outre, les performances gravement perturbees l'intervalle

avec l'intervalle

des rats trait.% a l'alcool &aient

lorsqu'un distracteur &ait

introduit durant

court. On discute ces rdsultats en les comparant aux dbfi-

tits de la u&moire a court terms des alcooliques chroniques et des Korsakoffs alcooliques.

Deutschsprachige ZuSammenfaSsUng: Es zeigte sich, dal3etn prolongierter Alkoholkonsum (20 Wochen), verbunde;mit entsprechender Ernghrung nach einer zweimonatigen alkoholfreien Periode zu einer residuaren Einschrlinkungdes KurigedZchtnisses fiihrte.Der Alkohol wurde in einer fltissigenDiltform verabreicht, deren Kaaus Alkohol bestanden. Eine Kontrolllorien zu 35 - '37 s/o gruppe erhielt die gleiche Digitnur mit dem Unterschied, daR Rohrzucker in gleicher Menge anstelle des Alkohols substituiert wurde. Eino zweite Kontrollgruppe erhielt eine in Pillenform zusammengestellte Nahrung; Nach einer 60 Tage dauernden alkoholfreien Periode wurde das Kurzzeitgedgchtnis gepriiftindem die Rattenaqf eine Zeitumkehraufgabe .trainiertwurden. Dabei wurden die Tiere bei alternierenden Versuchen beim Herunterdrtickeneiner Stange belohnt, Die Leistungen bei der Alternierungsaufgabe wurden ftir eln kurzes (20 Sekunden) und.fiirein langes (50 Sekungen) Retentionsintervall ausgewertet. WH?rend die alkoholbehandelten,Ratten relativ unbeeintrschtigt waren, wenn das Retentionsintervall kurz dauerte, waren sie schwer beeintrgchtigt bei langem IntervaIl. AuRerdem waren die Leistungen aer alkoholbehandelten Ratten such dann schwer gesttlrt, werin eine ablenkende Aufgabe wlhrend des kurzen Retentionsintervalles eingefiihrtwurde. Die Ergebnisse wurden im Vergleich.mit den Kurzzeitgedachtnisstidrungenvon chronischen Alkoholikern und alkoholischen Korsakow-Patienten diskutiert.