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D K Ingram

Publications and source records attributed to D K Ingram.

At least 145 records · Page 8Linked to original sources
PubMed1986

Effects of inescapable shock on maze performance as a function of age in mice.

The hypothesis was investigated that aged animals receiving an experimental treatment of inescapable shock would suffer greater deficits in swim T-maze performance than either their younger shocked counterparts or their age-matched nonshocked controls. Three age groups of male C57BL/6J mice were studied: (a) young-mature (8-9 mo); (b) middle-aged (15-16 mo); and (c) aged (26-27 mo). Equal numbers (n = 16) from each age group were assigned to either a treatment group, which received 3 days of inescapable shock (6 sec, 200 microA) during a 60-min session on a variable time schedule (VI-60 sec), or a control group, which was placed inside the apparatus for an equal amount of time. Beginning 24 hr after the last shock session, swim maze training consisted of 10 daily trials over 5 consecutive sessions. The hypothesis was partially confirmed with respect to the latency to swim to the choice-point of the T-maze. Only the aged treatment group demonstrated significantly impaired performance. With respect to the measure of learning (percent correct responses) in the alternation task, inescapable shock significantly impaired performance; however, the effect was a weak one and there was no evidence of differential impairment across age.

Aging↗
PubMed1986

Assessing the predictive validity of psychomotor tests as measures of biological age in mice.

Two experiments assessed the predictive validity of a psychomotor test battery in male C57BL/6J mice. First, performance was recorded for 66 mice in rotorod, tightrope, grip strength, exploratory activity, and runwheel activity tasks at 24 mo of age. Except in the rotorod task, performance was positively and significantly correlated to lifespan, i.e. better performance indicated longer lifespan. Body weight and body temperature were also significantly correlated with lifespan, while water consumption was negatively related. Using the five behavioral scores in a multiple regression analysis, about 40% of the variance in lifespan was explainable. When measures of body weight, body temperature, and water consumption were added to the regression equation, about 54% of the variance in lifespan could be explained. As revealed by factor analysis, a high degree of interrelationship existed among variables. In a second experiment, 54 mice were tested in the psychomotor battery every 8 weeks from 24 mo. Scores in the tightrope and both locomotor activity tasks revealed age-related declines, whether considering all individuals or only those surviving to 28 mo. Significant correlations between first and subsequent scores indicated stability of individual differences for tightrope and exploratory activity at most ages and for runwheel activity at 26 mo but not later. Rotorod and grip strength scores were not stable and suggested confounding by learning. Significant correlations with lifespan were obtained at some ages for all tests. In contrast to the first experiment, however, there were no significant correlations between lifespan and scores at 24-mo for any test and little correlation among scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1985

Relationship of body temperature stability to mortality in aging mice.

An age-related decline in the capacity for thermoregulation among homeothermic animals has been observed frequently under conditions of extreme ambient temperatures. We investigated the temporal stability of the internal body temperature of 69 C57BL/6J mice from 25 months of age until death in a controlled, neutral thermal environment. Estimates of temporal variability were calculated over consecutive 1-month intervals using (colonic) body temperature data collected weekly. The results of this longitudinal analysis indicated that the regulation of body temperature, as measured by its temporal stability, became increasingly less precise with advancing age. Body temperature exhibited a significant decline as the animal approached death. Individual differences in body temperature and the temporal regulation of body temperature were significantly correlated with lifespan, although the direction of the relations were opposite. Body temperature correlated positively with lifespan, whereas the temporal stability of body temperature correlated negatively with lifespan. Thus, animals exhibiting higher body temperatures and greater temporal stability also tended to live longer than their cohorts.

Aging↗
PubMed1985

Radial maze performance in young and aged mice: neurochemical correlates.

Young (8 month) and aged (27-28 month) male C57BL/6J mice were trained in a spatial discrimination task requiring working memory. The mice were tested during three trials daily in an eight-arm radial maze for 36 test days. Correct choices were reinforced with isotonic saline. In contrast to past reports, young mice learned the task. Old mice also learned the task, and no significant age-related differences in performance were observed. Following maze training, the mice were killed, the brains removed, and the specific activities of choline acetyltransferase (E.C.2.3.1.6., ChAT) and L-glutamic acid decarboxylase (E.C.4.1.1.15., GAD) were assayed in the hippocampus, and in frontal, sensorimotor, and cingulate areas of the cerebral cortex. The activities of these neurotransmitter synthetic enzymes did not differ significantly between young and old mice. Correct responding in the radial maze was positively correlated to ChAT activity in the cingulate cortex and negatively correlated to ChAT activity in the sensorimotor cortex. There was a similar pattern of correlation between performance and regional GAD activity, although none of the correlations involving GAD reached statistical significance.

Aging↗
PubMed1985

Effect of intermittent feeding on thermoregulatory abilities of young and aged C57BL/6J mice.

At 6 mth of age, male C57BL/6J mice were subjected to an intermittent schedule of feeding (every-other-day) or continued to be maintained on an ad libitum diet (24% protein). This regimen of dietary restriction resulted in increased mean and maximum lifespan (11%) compared to the survival of ad libitum-fed mice. At 8 and 26 mth of age, different groups of mice were tested for cold tolerance during 3 h exposure to 10 degrees C. Aged mice (26 mth) fed ad libitum compared to young mice (8 mth) on the same diet had significantly lower baseline colonic temperatures prior to cold exposure, and impaired cold tolerance, as measured by the rate of decline in colonic temperature during cold exposure. Dietary restriction by intermittent feeding had no significant effect on cold tolerance in young mice or baseline colonic temperature in young or aged mice. However, the cold tolerance of aged mice subjected to 20 mth of intermittent feeding was markedly improved over that of aged cohorts maintained on an ad libitum diet and in fact was indistinguishable from that of young counterparts. Thus, it appeared that this regimen of dietary restriction when implemented in young adults prevented the age-related decline in cold tolerance observed among ad libitum fed mice of this strain.

Adaptation, Physiological↗
PubMed1985

Effects of intermittent feeding on neurochemical markers in aging rat brain.

Male Wistar rats were fed a diet of 24% protein either ad lib (AL) or every other day (EOD) beginning shortly after weaning. Rats were killed at 6 or 24-months of age. The corpus striatum, cerebral cortex, hippocampus, and cerebellum were assayed for muscarinic cholinergic receptor binding and the activities of choline acetyltransferase (ChAT), L-glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH). Sensecent rats maintained on EOD feeding schedules from weaning showed a markedly higher density of striatal muscarinic binding sites and higher activities of cerebellar, hippocampal, and striatal ChAT, as compared with values in AL-fed rats. Regional GAD and TH activities were relatively unaffected by EOD feeding; however, at 6 months, EOD-fed rats had higher cortical GAD and lower cortical TH activities than corresponding AL-fed rats. EOD feeding for only 2 weeks produced no significant effects on neurochemical parameters examined in 24-month-old rats. We conclude that EOD feeding from weaning can alter neurochemical markers of senescence in rat brain; that cholinergic systems are affected in particular; and that the observed alterations produced by EOD feeding represent chronic rather than acute effects.

Aging↗
PubMed1985

Discrimination learning requiring different memory components in rats: age and neurochemical comparisons.

The performances of young (8-9 months) and aged (22-24 months) male ACI rats were compared in a T-maze requiring two discriminations, each of which placed different demands on memory processing. A spatial discrimination in the stem of the T-maze required long-term reference memory; a discrete-trial, alternation discrimination in the arms of the T-maze required working memory. Following acquisition training in one maze, rats were also trained in a second maze at a different location in the room. The correct response in the stem of this maze was opposite to that in the first maze. In two experiments with slightly different pretraining procedures, similar results demonstrated that aged rats made more errors in all phases of maze training than did their young counterparts. The results suggest that all components of memory processing were affected equivalently because the age-related impairment was not selectively greater in any component of the task. In a third experiment, aged rats were unimpaired in the ability to perform in a T-maze task involving a brightness discrimination with intramaze cues. This result suggests that the age-related impairment in the two-component T-maze task was restricted to the cognitive demands of the task. Neurochemical analyses were performed to determine whether regional neurotransmitter synthetic enzyme activities could be used to identify neurochemical systems associated with performance in these tasks and with any age-related impairments observed. Choline acetyltransferase and glutamic acid decarboxylase were assayed as markers for cholinergic and GABAergic systems, respectively, in the hippocampi and the following cortical regions: frontal, sensorimotor, auditory, cingulate, occipital, and pyriform-perirhinal. A slight (8%) but significant age-related decline was observed in the activity of glutamic acid decarboxylase but not of choline acetyltransferase. Although the correlation between maze performance and regional enzyme activities generally supported several previous observations, the only significant correlation to emerge was between working memory performance and glutamic acid decarboxylase activity in the cingulate cortex.

Aging↗
PubMed1984

Delayed loss of striatal dopamine receptors during aging of dietarily restricted rats.

Dietary restriction by feeding every other day retards the normal age-associated loss of dopamine receptors from the corpus striatum of the rat. Ad libitum fed animals lose about 40% of the receptors labeled by [3H]spiperone between 3 and 24 months, while the loss is only about 20% over the same period in restricted rats. Ultimately, by 30 months of age, values for restricted animals drop to those of 24-month-old ad libitum-fed rats. The mean lifespan of restricted rats, however, is about 40% longer than the 22-24 months characteristic of ad libitum-fed counterparts. The effect of restriction appears to be chronic rather than acute since ad libitum-fed rats which are restricted for 2 weeks prior to sacrifice possess receptor levels comparable to 24-month-old rats maintained on ad libitum feeding for their entire lifetime.

Age Factors↗
PubMed1983

Methadone in brain and its effects on locomotor activity of young and aged mice.

Plasma and brain levels of methadone produced by subcutaneous injections of the chloride salt (7.5, 15.0 or 22.5 mg/kg) and resultant changes in locomotor activity were determined in young (6-8 months) and aged (30-32 months) C57BL/6J mice. Methadone elevated locomotor activity of young and aged mice above control levels to about the same extent. The degree of activity elevation was inversely related to dose for both age groups, however, the reduction in stimulation with increasing dose was greater for young than aged mice; and only young mice exhibited a significant biphasic response to the high drug dose. Although the behavioral results suggest that aged mice were less responsive than young mice to methadone, brain concentrations of the drug were higher in aged than young mice by approximately one hour after injection. The age difference noted in brain concentration was not observed for plasma levels of methadone; hence cannot be accounted for by reduced drug metabolism in aged mice. The results of this study indicate that compared to young adults, aged mice are less responsive behaviorally to methadone despite higher brain concentrations of the drug.

Aging↗
PubMed1983

Life-long dietary restriction affects striatally-mediated behavioral responses in aged rats.

The effects of life-long dietary restriction on rotational behavior and stereotypy induced by intrastriatally administered dopamine-excitatory (dopamine, DA; amphetamine, AMPH) or cholinergic inhibitory (atropine, AT) agents were examined in rats. Three groups of male Wistar rats were used; mature ad lib (YAL, 6 month), old ad lib (OAL 24 month), and old restricted animals (OR). OR animals were fed and fasted on alternate days from weaning. Each rat was unilaterally lesioned in the left substantia nigra with 6-hydroxydopamine and a cannula was implanted in the right caudate nucleus. Several doses of each drug [AT (0, 1, 7, micrograms) DA (0, 5, 50 micrograms), and AMPH (0, 2, 5, 5, 10 micrograms)] were given randomly (1 dose/day with 1 week between drugs). All doses of a particular drug were given before the next drug regimen was started. A combination of AMPH (25 micrograms) and AT (1 microgram) was also administered in one injection at the completion of all other regimens. Results showed that OR animals responded as well as YAL animals and far better than OAL animals following AMPH, DA, or low doses of AT. However, both the high dose of AT and the combined dose of AMPH-AT seemed to suppress responding in OR animals. Neither AT alone or AMPH-AT combinations had effects in OAL animals. Results are discussed in terms of the possible specificity of effects of dietary restriction on striatal functioning and behavior in senescence.

Aging↗
PubMed1983

Methadone effects on locomotor activity of young and aged mice.

The effect of age on the behavioral response to methadone hydrochloride was examined in male C57BL/6J mice. After 1 hr habituation to an oval runway, locomotor activity of young (6-8 months) and aged (30-32 months) mice was monitored for 3 hr following injections of saline or methadone hydrochloride (2.5, 7.5, 15.0 or 22.5 mg/kg). The three highest doses initially elevated activity which then declined over the next 1 1/2 to 2 1/2 hr. Compared to young mice, activity of aged mice was elevated less extensively, but remained elevated for a longer period of time. The attenuated elevation could be interpreted in terms of reduced physical capacity of aged mice; however, the more prolonged elevation was clearly an age-related difference in reaction to the drug. Although the mechanism accountable for this effect is unknown, it is not likely related to age differences in drug absorption or distribution to active sites.

Age Factors↗
PubMed1983

Age-dependent correlation of motor performance with neurotransmitter synthetic enzyme activities in mice.

The performance of male C57BL/6J mice (Mus musculus) was assessed in a battery of tests designed to detect age-related losses in motor abilities and also to examine individual differences within age groups. Studied were 4-, 18-, and 24-month-old mice. Within 5 days following the completion of the behavioral battery, the mice were killed, and brain tissue was taken for determinations of choline acetyltransferase (EC 2.3.1.6), L-glutamic acid decarboxylase (EC 4.1.1.15) and tyrosine hydroxylase (EC 1.14.16.2) activities in the frontoparietal + temporal + occipital cortex, hippocampus, striatum, and cerebellum. Two composite test scores were derived for each animal. The first composite score comprised measurements of locomotor activity, and the second reflected strength and coordination abilities. Test scores included in each composite correlated highly with that composite score, but not with the other composite. This observation suggests that there is a high degree of internal consistency for the composite scores and that the composite scores represent independent behavioral factors. Significant correlations between the composite scores and regional enzyme activities were detected; these correlations varied with age. In most cases, the sign (+, -) of the correlation was reversed at 24 months as compared with 4 months of age. These results suggest that the relations between performance and enzyme activities vary with age, and may reflect altered neurotransmitter function during senescence. This work serves as an example of how direct correlational analyses may help to elucidate behavioral-neurochemical interactions in aging.

Aging↗
PubMed1983

Effects of intermittent feeding upon growth, activity, and lifespan in rats allowed voluntary exercise.

From weaning until death, male Wistar rats were housed in activity-wheel cages with one group maintained on an ad libitum (AL) diet and another provided the diet every-other-day (EOD). EOD-fed rats had a mean lifespan of 124 weeks compared to 103 weeks for AL-fed rats. While post-weaning body weight and growth rates were reduced among the EOD-fed animals compared to AL-fed animals, there was no significant difference in growth duration. Positive correlations were observed between lifespan and estimates of growth rate and duration in the AL group but not in the EOD group; thus, little evidence was produced to support the hypothesis that growth rate is inversely related to longevity. While the EOD feeding regimen resulted in higher activity levels later in life, wheel activity levels were actually lower in this group in early life compared to the AL group. The observation of reduced wheel activity among young rats fed EOD was replicated in a second experiment. Thus, little support was obtained for the hypothesis that increased activity mediates the beneficial effects of dietary restriction on longevity, unless this mechanism is active late in the lifespan.

Animals↗
PubMed1983

Toward the behavioral assessment of biological aging in the laboratory mouse: concepts, terminology, and objectives.

The thesis is presented that much of the controversy and confusion concerning the measurement of biological aging stems from the lack of agreement on clearly defined objectives, constructs, and methods to validate measures. To alleviate some of the confusion, basic terminology borrowed from psychometrics is offered to provide a conceptual framework within which such issues can be discussed. This psychometric nomenclature is subsequently applied to the development and evaluation of a test battery designed to assess biological aging in laboratory mice at a behavioral level of analysis. Reference is made to the assessment of reliability, content validity, construct validity, and predictive validity of tests of biological aging.

Aging↗