Relative aversion thresholds for shock in infant mice

Using a spatial-preference technique, we tested separate groups of mice, 5, 7, 9, 11, 13, and 15 days of age, for escape and avoidance of a range of shock intensities administered from AC constant current and fixed impedance shock sources. With intensities ranging from 0 to .2 mA and to 70 V for the respective sources, near asymptotic escape and avoidance were obtained at .1 mA and at 50 V for all ages tested. Although few differences in the relative aversiveness of particular shock intensities were noted across ages with each source, the fixed impedance source produced more consistent avoidance than did the constant current source. The findings suggest that the motivational properties of shock remain relatively constant throughout the early development of the mouse and that the technique employed in this study should prove useful in assessing possible age-related alterations in sensitivity to shock as a result of physiological or pharmacological manipulations.     

Escape learning in infant mice as a function of drive level and drive shifts during acquisition

Separate groups of 9-day-old Swiss-Webster mice began straight-alley escape training at .1 or .4 mA. After 12 trials, half of the mice in each group were shifted to .4 or .1 mA, respectively, whereas the remaining half continued at their orginal level for an additional 12 trials. Twenty-four hours later, half of each of the 4 shock-level groups were retested at .1 mA, half at .4 mA. The result indicated that those groups which made a large number of competing responses during early trials and showed a gradual reduction over training trials (.1-.1 and .1-.4) emitted the fewest number during retest at either shock level. In contrast, those groups with either limited (.4-.1) or no (.4-.4) opportunity to decrease competing responses during training showed evidence of poor (.4-.1) and no (.4-.4) retention of learned inhibition of that response. Running speed was clearly a performance measure, as it only reflected existing shock levels during both training and retention trials.     

Age-associated learning and memory deficits in two mouse versions of the Stone T-maze

We have previously reported that a modified Stone T-maze (STM), using escape from water as motivation, was effective in evaluating learning and memory ability in young C57/BL6 mice. Here we report on the effectiveness and sensitivity of the STM in the assessment of age-related learning and memory deficits in mice using either escape from foot shock or water as the motivational manipulations. C57BL/6Nia mice 7-, 12-, 20- and 24-months old received 15 massed trials in the escape from foot shock motivated STM while C57BL/6Nia mice 5-, 12-, and 25-months old were tested in the escape from water STM. Analysis of errors, the main performance variable, revealed similar results in both versions of the task with younger mice making fewer errors. Notably, mice of all ages in the water-motivated version moved quickly through the maze, while all ages of mice in the shock-motivated version tended to wait for shock to be initiated to move forward. Overall, both versions of the STM appear to be sensitive to age-related changes in learning and memory and provide an alternative to other testing paradigms such as the Morris water maze which are susceptible to performance confounds which can lead to uninterpretable results.     

Inception of a 24-hr capacity memory in two mouse strains

Separate groups of C3H and Swiss-Webster (S-W) mice received 25 escape training trials in a straight alley at 8 or 10 days of age. Each of these groups was then divided into 3 retention groups, receiving an additional 25 training trials, 1, 6, or 24 hr following original training. Comparisons of the retest scores with original training scores, as well as with litter-mate controls without prior training, indicated that both strains trained at 8 days of age failed to demonstrate retention of learning when retested 24 hr after training, although they showed reliable 1-hr retention and some evidence of 6-hr retention. However, mice trained at 10 days of age performed better on the retention tests at all retest intervals than they had on original training, as well as better than maturation controls without prior training. These results indicate that a 24-hr retention capacity for escape training develops between 8-10 days of age in both mouse strains.     

Shock controllability and opioid substrates of escape performance and nociception: differential effects of peripherally and centrally acting naltrexone

Rats exposed to inescapable shock exhibited analgesia and a significant impairment of shock-escape learning in a shuttle box situation 24 hr later. In contrast, rats exposed to escapable shock or to no shock displayed neither effect. Naltrexone (10 mg/kg) significantly reduced the analgesia and completely eliminated the escape deficit in inescapably shocked rats but induced hyperalgesia, coupled with a marked deterioration of escape performance, in escapably shocked and nonshocked rats. The same dose of quaternary naltrexone, which has low ability to cross the blood-brain barrier, had no effect on either the antinociception or the escape deficit produced by inescapable shock, although it also induced escape impairment and hyperalgesia in rats preexposed to escapable shock or to no shock. A second experiment demonstrated that both the escape interference and the antinociceptive consequences of prior inescapable shock could be reduced partially by a much lower dose (1 mg/kg) of naltrexone but 50 times this amount of quaternary naltrexone was still without effect. These results imply that the consequences of exposure to inescapable shock are mediated by activation of central opioid processes whereas naltrexone-induced effects in escapably shocked and nonshocked animals may be peripherally mediated. The relevance of these findings to the possible role of nociception in escape performance is discussed.     

Aged and adult rats compared in acquisition and extinction of escape from the water maze: focus on individual differences

Individual differences in water maze and open-field performance of aged and adult rats were compared in a cross-sectional study. Three- and 24-month-old rats were classified into superior, moderate, and inferior groups on the basis of escape latencies during hidden platform acquisition and were compared regarding water maze acquisition and extinction, and open-field behavior. Unexpectedly, subgroup differences were invariant across age: The inferior and superior maze learners differed in (a) thigmotactic swimming during water maze acquisition and extinction and (b) open-field rearings. Thus, although aging has a detrimental effect on water maze acquisition and extinction, the degree of impairment might be partly determined by individual novelty-induced rearing activity and thigmotactic swimming at adult ages.     

Development of 24 hour retention of escape learning in neonatal C3H mice

The development of 24-hr memory of an escape response in neonatal C3H mice was examined in 2 experiments. In experiment 1, separate groups of mice received 25 trials of escape training for 3 consecutive days (24 hour Inter-session-interval) beginning at 5, 7, and 9 days of age. Several different measures demonstrated witin-session improvement for all ages on all test days. However, between-session improvement which was not due to maturation did not occur until after 9 days of age. In experiment 2, separate groups of mice received 25 escape training trials at either 8 or 10 days of age, and were retested 24 hrs later. Comparisons of the retest scores with original training scores as well as with littermate controls without prior training experience, showed that 8-day old mice failed to show retention effects of prior training, whereas 10-day old mice performed better on the retention test than they had on original training, as well as better than controls without previous training. The results suggest that 24-hr memory of the escape task develops at 9–10 days of age in the C3H mouse.     

Hypothermia-induced retrograde amnesia in mature and aged rats

Mature (10-month-old) and aged (25-month-old) rats were trained on a passive avoidance task. Following training, rats in each age group were exposed to a hypothermia treatment, restraint alone, or no treatment. The hypothermia treatment involved immersing the mature rats in 4°C water for 12 min and immersing the aged rats in 1°C water for 12 min. This treatment reduced the body temperature of both age groups to an equivalent temperature (22°C). Following immersion, the body temperature of the aged rats continued to decline to a lower level and recovered at a slower rate than the mature rat's temperatures. When all rats were tested 24 hr after training for retention of the avoidance task, mature rats performed better than aged rats when trained with the same shock intensity. Increasing the shock duration for the aged rats eliminated the performance differences on the passive avoidance task between ages. Rats exposed to hypothermia showed poorer retention of the task (i.e., retrograde amnesia) than all control conditions. However, no age differences in the degree of amnesia induced by the hypothermia treatment were apparent once age groups were equated on the intensity of the amnesic agent (hypothermia) and degree of initial learning.     

Stressor-provoked behavioral changes in six strains of mice

Behavioral changes induced by inescapable shock were examined in six strains of mice. Exposure to shock provoked time-dependent disturbances of shuttle escape performance. In some strains the shock treatment did not affect escape performance, whereas in others profound performance deficits were evident. The inescapable shock treatment likewise induced strain-dependent alterations of performance in a forced-swim task. In most instances the shock treatment initially provoked invigorated responding, but in other strains the shock had no effect or depressed active responding. Finally, Y-maze spontaneous alteration performance was not affected by the shock treatment, although a strain-dependent increase of perseverative responses was evident. The occurrence of a stressor-induced deficit in one task in a particular strain of mouse was not predictive of behavioral alterations in a second task. These data are discussed with respect to animal models of depression and genetic differences associated with the response to stressors.     

Age effects on passive avoidance behavior of vasopressin-deficient Brattleboros

Experiments in which vasopressin-deficient Brattleboros were tested in a passive avoidance procedure have yielded contradictory results. Some investigators observed the passive avoidance behavior of these subjects to be inferior to that of normal controls, while others failed to observe such differences. Inspection of the literature suggested that age differences between subjects which participated in these experiments might be responsible for the discrepancy. In the present experiment, HO-DI and HE Brattleboro rats of different ages were tested in the standard passive avoidance task. Passive avoidance performance of HO-DIs was, indeed, influenced by the age of the subject at the time of testing; HO-DIs reentered the shock compartment sooner than HE at 35 days, but later than HE at 120 days. There was no difference between the two groups of subjects at 60 days. The percentage of HO-DIs which reentered the shock compartment on the post-shock trial decreased with increasing age.     

Circadian rhythmicity and behavioral depression: I. Effects of stress

Rats were exposed to repeated sessions of inescapable footshock, and behavioral depression was subsequently assessed by measuring escape performance during exposure to escapable shock in a different testing environment. Free-running circadian activity rhythms were assessed using running wheels for approximately three weeks before and after administration of inescapable shock. Several animals showed lengthening of free-running period and decreases in activity level following shock. Similar effects were also seen in rats that were removed from their running wheels, placed within the shock apparatus, and not given shock, but not in nonhandled control animals. Furthermore, period lengthening in shocked and handled rats was positively correlated with escape performance, suggesting that circadian rhythm alterations occurred in those animals that were best able to cope with shock or handling-related stressors. In contrast, individual differences in circadian period and activity level during baseline conditions were not predictive of either escape performance or circadian rhythm alterations. These results suggest that successful behavioral adaptation to stress may be associated with alterations of circadian rhythmicity.     

A genetic analysis of escape behavior in rats

Three strains of highly inbred rats and their derived F₁ hybrid progeny were tested for escape latencies in a novel test situation at three ages. There were very highly significant differences in escape latencies between genotypes and between ages. There was also a very highly significant genotype by age interaction; the inbreds had increasing latencies with increasing age, whereas the hybrids did not. Heterosis was observed, and it was concluded that this behavioral heterosis was consistent with the hypothesis of selection for an intermediate optimum in latency to escape.     

Sex differences in the behavioral consequences of inescapable footshocks depend on time since shock

In two experiments, the effects of inescapable shock on subsequent shuttle-box escape performance were studied in male and female rats. Effects of treatment with short-duration shocks (2 s) were studied after 1- and 24-hour intervals (Experiment 1), and effects of long-duration shocks (6 s) were studied after 24- and 72-hour intervals (Experiment 2). Experience with inescapable shock resulted in a serious disruption of escape performance in both males and females. A large increment in escape latencies was found both during fixed ratio 1 and fixed ratio 2 escape training; however, effects of inescapable shock were more pronounced in males than in females. In Experiment 1, sex differences were most obvious after the short 1-hour interval whereas, in Experiment 2, sex differences were only present after 24 hours and not after 72 hours. Shuttle activity during 2-min adaptation prior to shock-escape training was reduced in both males and females treated with IS, and this effect was somewhat stronger in males than in females. The data of these experiments show that male rats are more sensitive to the consequences of exposure to inescapable aversive stimulation than female rats. It is proposed that the time-dependency of the sex differences in behavioral consequences of treatment with inescapable shock may be related to sex differences in transient neurochemical or hormonal changes induced by inescapable shock.     

Two months makes a difference in spatial orientation learning in very old FBNF1 rats

Age-related changes in cognitive performance may be more pronounced in the period near or exceeding the median life span. Therefore, we compared the acquisition of a Morris water escape task by two groups of very old Fischer344 x Brown Norway hybrid rats. The mean age difference between the two groups of rats (a 33- to 34-month-old group versus a 35- to 36-month-old group) was about 2 months. Both groups of rats initially had the same level of performance, but then the younger group learned to escape onto the submerged platform faster, swimming a shorter distance, than the older group. By the fifth acquisition session, the younger rats needed only half the time and swam a shorter distance before they reached the platform than the older rats. These differences in learning were not due to different locomotor abilities as both groups had a similar swimming speed. These results suggest that age-related changes in cognitive performance are indeed more pronounced in the period around the median life span. We also discussed different set-ups to perform cross-sectional age-comparison studies. If there are not sufficient animals from one batch, it may be worthwhile to combine animals from different batches per age group, provided that breeding, rearing, housing, and testing conditions are highly standardized.     

Ontogeny of short- and long-term memory capacities for passive avoidance training in undernourished mice

To assess the effects of early postnatal undernutrition upon the developing abilities of infant and juvenile mice to acquire and retain a passive-avoidance response, we reared mice following birth in either “normally nourished” or “undernourished” conditions by maintaining litter sizes of 6 or 16, respectively. At ages ranging from 7 to 21 days of age, mice from each nutritional condition were trained to withhold stepping off from a small vibrating platform in order to avoid shock. Following training to a common criterion, separate groups of mice were retrained to the same criterion either 1 or 24 hr later. From the comparisons with yoked control groups at each age and retention interval, we conclude that although undernutrition results in some age-related differences in the ability to withhold responding, these are quite small during acquisition within each age group. In contrast, the retention data suggest that undernutrition delayed the development of both short- and long-term memory abilities on this task. In general, these results are similar to earlier data involving discriminated shock-escape wherein undernutrition had little apparent effect upon acquisition at the early ages but rather marked effects upon developing memory systems.     

Evolution of three lymphocyte markers in newborn, preterm infants.

Nine newborn, preterm infants have been studied at the ages of 1-3 days, 8-10 days and 22-24 days for surface markers on peripheral blood lymphocytes. As compared to adult controls, four of the infants had a low proportion of sheep RBC binding lymphocytes at birth, but at 1-3 weeks of age all infants had reached the adult level. Lymphocyte receptors for Fc of IgG and for complement, although both mainly characterizing non-T cells, evolved differently post partum: the proportion of Fc-receptor-bearing lymphocytes tended to increase with age of the infant, whereas already at birth complement receptor-bearing lymphocytes were at or above the adult level.     

The development of naming and word fluency: evidence from Hebrew-speaking children between ages 8 and 17

Naming and word fluency tests are commonly used in neuropsychological evaluations of both children and adults. The current work examines at which age performance on these tests reaches adult level. One hundred fifty children, 30 in each of 5 age groups (8-9, 10-11, 12-13, 14-15, 16-17), and 30 adults ages 18 to 29, participated in the study. Participants completed a Hebrew naming test, a three-letter phonemic fluency task, and a three-category semantic fluency task (animals, fruits and vegetables, and vehicles). Results show that all measures increase steadily from age 8 to age 17. No difference between the 16- to 17-year-old adolescents and the adults was found on the naming test and on the phonemic fluency task, but such a difference was documented for semantic fluency. The relative contribution of the maturation of vocabulary and the development of efficient retrieval processes to performance on naming and fluency tasks is discussed.     

Age-related changes in spontaneous behavior and learning in NMRI mice from maturity to middle age

Spontaneous behavior and learning and memory of 3-, 6-, 9- and 12-month-old virgin female NMRI mice were compared. Open field activity and spontaneous alternation in a Y-maze decreased in an age-related manner, reaching a statistical level of significance for the groups aged 9 and 12 months. Spatial learning was highly impaired in 9-and 12-month-old mice in the place version of a Morris-type water maze but not in the cued version of this task. Changes in motor activity, swimming ability or speed did not appear to account for these deficits. In a one-trial passive avoidance, performance was more variable, although a deficit in the oldest age group was clearly evident using a cutoff time of 120 sec. The passive avoidance was not attributable to reduced shock sensitivity. Together, these results suggest that the onset of aging in NMRI mice occurs at the age of 9 and particularly 12 months. NMRI mice of this age could, therefore, represent a viable animal model for the study of cognitive impairments in aging.     

Acquisition and retention of a passive-avoidance task as a function of age in mice

In Experiment I groups of mice between 16 to 100 days of age were tested for retention of a passive-avoidance response between 1 min and 96 hr following a single training trial at 2 shock intensities. In general, although almost all age groups displayed reliable retention at all retest intervals, some retention losses were found among the youngest age groups at the longer retention intervals. Higher shock intensity resulted in longer retest latencies, primarily among the youngest mice. In Experiment II mice 16, 25, and 100 days of age were trained to criterion on the passive-avoidance task and retested on a single trial following retention intervals of 24, 96, 192, and 384 hr. Young mice exhibited severe retention losses relative to 100-day-old mice at the longer intervals, even though they did not show deficiencies in acquisition. Neurological maturity at the time of original training appears to account for the age-related memory differences.     

The effects of life-long food restriction on spatial memory in young and aged Fischer 344 rats measured in the eight-arm radial and the Morris water mazes

The effect of life-long 60% ad lib food restriction on performance in two tasks involving spatial memory, the eight-arm radial maze and the Morris water maze, was studied in young and aged Fischer 344 rats. Restricted (R) and ad lib (AL) feeding groups were compared at 8, 16, and 24 months of age on both tasks. A 30-month-old R group was also tested in the Morris water maze. In the eight-arm maze, although 24-month-old animals performed more poorly than 8- and 16-month-old animals during the first week of testing, overall accuracy of performance did not vary significantly as a function of age. Twenty-four-month-old animals took longer to make 10 choices than did younger animals, and there was a significant interaction between feeding regimen and age, reflecting the fact that at the two younger ages, R groups performed more quickly than the AL groups. In the Morris water maze, both distance swum and time to find the platform increased with age. Life-long food restriction led to small but significant improvements in performance in the water maze in aged rats. R groups showed evidence for better retention over 24-hour intervals than did AL groups. By 30 months of age, however, R animals showed impaired performance relative to younger R groups. These differential findings on the two tasks, as they were used here, suggest that there was greater impairment with age on the spatial memory task requiring retention of information over long intervals than there was on the task primarily involving working memory within a trial. Life-long food restriction would appear to delay the impairments of age, but not prevent them.