Z. Michael Nagy

Development of behavioral arousal and inhibition in the Swiss-Webster mouse

The development of behavioral arousal was examined in mice ranging from 9 to 100 days of age. An inverted U-shaped ontogenetic activity curve was obtained, consistent with past studies of other altricial rodents. However, the peak in the activity curve for the mouse occurred at 13 days of age, at least 2 days earlier than reported for the rat and hamster. The findings are interpreted as indicating that the onset of behavioral inhibitory capacities occur earlier in the mouse and are discussed in relation to development of brainstem arousal and forebrain inhibitory biochemical systems.

GABA-mediated behavioral inhibition during ontogeny in the mouse.

Although immature rats and mice generally demonstrate poor behavioral inhibitory capacities, some recent evidence may indicate the presence of substantial inhibitory control. The present experiment investigated the possibility that gamma-aminobutyric acid (GABA) systems may mediate some behavioral inhibition during early development. Mice 9 – 100 days old were injected with the GABA-elevating agent amino-oxyacetic acid (AOAA) and tested for behavioral activity. High levels of locomotor activity characteristic of immature control mice were attenuated following AOAA injection, whereas AOAA had little effect on the activity of adult mice. Moreover, AOAA produced a period of rebound hyperactivity for young but not for adult mice. These findings suggest that although GABA systems may mediate early behavioral inhibition, coordination between excitatory and inhibitory capacities matures slowly. In a second experiment the dopamine-β-hydroxylase inhibitor FLA-63 prevented rebound hyperactivity in young mice pretreated with AOAA, suggesting that the excitatory component may be mediated by noradrenergic systems.

Development of cholinergic inhibitory capacities in the hyperthyroid mouse

The ontogeny of behavioral arousal and inhibition, as measured by spontaneous locomotor activity, was compared in four experiments for controls and mice injected with thyroxine as neonates. Mice treated with thyroxine at 1-3 days of age had higher activity levels at 10-15 days of age than controls, suggesting potentiation of arousal systems by the hormone treatment. Although thyroxine-accelerated development had no reliable effect upon the age at which peak activity occurred, scopolamine injections increased activity as early as 15 days of age in thyroxine-treated mice, whereas saline-treated or unhandled controls did not show a similar increase until 16-17 days of age. The findings were interpreted as indicating both a potentiation of arousal and a compensatory acceleration of cholinergic inhibitory capacities as a result of the neonatal hyperthyroidism. In addition, the importance of the behaviorally suppressive effects of a novel injection experience in the neonatal mouse was demonstrated.

Differential development of 24-h retention capacities for two components of T-maze escape learning by infant mice

At 9 or 11 days of age, separate groups of Swiss-Webster mice received 12, 24, or 40 training trials to the goal opposite their first-trial choice in a shock-escape T-maze task. All groups were retested to the same goal for 25 trials 24 h following training, while maturation controls without prior exposure were trained to the goal opposite their first choice. All groups demonstrated increased escape proficiency during original training on two separate escape components: reaching the choice point and making the correct turn at the choice point. During retention testing, all groups at both ages exhibited better escape performance in terms of reaching the choice point than their maturation controls. However, when escape was measured in terms of choice, none of the groups trained at 9 days of age differed significantly from maturation controls when retested at 10 days of age. In contrast, retention of correct choice point turn varied directly with number of original training trials for mice trained at 11 days of age.

Comparison of behavioral activity in two apparatus for food-deprived mice

Behavioral arousal induced by food deprivation is well documented for rats tested in activity wheels, but activity levels may vary considerably for other species and when testing is done in other types of apparatus. The present study compared behavioral activity of ad-lib and food-deprived mice, as few studies have examined the effects of food deprivation in this species. Separate groups were tested continuously in activity wheels or 2 h daily in shuttle cages. Deprivation increased behavioral activity in both apparatus. The daily 2-h shuttle cage test proved to be a reliable and economical measure of deprivation-induced behavioral arousal in mice.

Open-field activity of retinal regenerate C3H mice: Further evidence of some visual capacities

Six groups of rd C3H mice were tested in the open field under various illumination conditions for 4 consecutive days. Two groups were tested under either a high or low level of illumination on each day, while the other groups were exposed to an illumination change following the first of 2 test minutes. Two groups received a 1-sec change to the other level and then a return to the original illumination level. The two remaining groups received the entire second minute of testing at the other illumination level. The finding that activity changed in a predictable direction as a function of the illumination change suggests visual functioning of some degree in this strain.

Potentiation of locomotor activity by d-amphetamine in infant Swiss-Webster mice

Swiss-Webster mice were tested for locomotor activity in either an electromagnetic field (5, 7, or 9 days of age) or photocell shuttle (9, 11, or 13 days of age) apparatus over a 4-h period following systematic injections of d-amphetamine or saline. While d-amphetamine reliably increased activity at all ages tested, the magnitude of the increase varied both as a function of age and apparatus, with younger mice showing a smaller increment than older mice in each apparatus and the electromagnetic field showing relatively greater increments than the photocell apparatus. In addition, amphetamine-induced hyperactivity for the age groups tested was always of longer duration than that reported for adult mice and rats, regardless of the type of apparatus. The present findings for mice are consistent with those that demonstrated that rats respond to amphetamine at early ages and also indicate that both species show similar age differences in the temporal effects of systematically administered amphetamine.

Neonatal hyperthyroidism alters the development of behavioral arousal and inhibition in the mouse

Thyroxine injections of neonatal mice at 1,2, and 3 days of age yielded higher activity levels during the second and third postnatal weeks compared to saline controls, but did not result in an earlier ontogenetic activity peak, which would have been indicative of accelerated development of inhibitory functioning. However, in the second experiment, hyperthyroid mice demonstrated a significant increase in activity following scopolamine injection as early as 15 days of age, whereas controls showed a similar increase at 17 days of age. This finding suggests that neonatal hyperthyroidism results in earlier development of the cholinergic system.

Effect of drive level upon age of onset of 24-h retention of discriminated escape learning in infant mice

Mice, 9 and 11 days old, received 24 training trials in a T maze to the goal opposite their first-trial choice at either.1- or.2-mA shock levels. Half of the mice within each age and shock level group were retested 24 h later at the training level, the remaining half were retested at the other shock level. Maturation controls without prior training were also trained under each of the retest conditions for previously trained groups. The training results indicated that while 11-day-old mice made more correct turns than 9-day-old mice, both age groups showed comparable rates of improved performance over trials independent of shock level. Upon retest, mice trained at 11 days of age demonstrated significant retention of the previously trained correct goal, while mice trained at 9 days of age did not differ from controls. This age-related difference in retention was independent of shock level during both training and retest trials.

Instrumental escape learning in neonatal c3h mice.

Five groups of C3H mice, 3-11 days of age, were given 25 trials in a straight-alley shock-escape task. Improved performance was indicated by a decrease in the number of competing responses made over training trials by all age groups and by an increase in the number of trials on which no competing responses occurred for groups 5-11 days of age. Running speeds appeared to reflect differences between age groups in the development of motor abilities rather than in learning capacities. These results support previous research indicating successful escape learning in neonatal mice and rats 5 days of age and extend this general finding to C3H mice as young as 3 days of age.