Reactivity to novelty in cognitively-impaired and cognitively-unimpaired aged rats and young rats

doi:10.1016/S0306-4522(97)00464-8

Neuroscience

Volume 83, Issue 3, 5 January 1998, Pages 669-680

https://doi.org/10.1016/S0306-4522(97)00464-8 Get rights and content

Abstract

Two distinct populations of aged, Long–Evans rats can be identified on the basis of performance in the Morris water maze task. Aged (24 month) unimpaired rats perform similarly to young (six month) animals. Aged, impaired rats display latencies to find the submerged platform greater than two standard deviations from the mean of the young animals. A hallmark of efficient cognitive processing is the ability to cope with environmental change. Consequently, the present studies were conducted to assess if aged, impaired animals display differential reactivity to repeated exposure to novel stimuli. Reactivity was assessed by examining the degree of (i) consumption of a novel gustatory/olfactory stimulus (sweetened milk), (ii) pain inhibition induced by exposure to a novel hot-plate (48.5°C) apparatus and (iii) exploratory behaviour in an elevated plus maze and a novel open field. Aged, impaired rats exhibited lower milk consumption on day one and protracted reactivity (lower consumption over days two to eight) in comparison to aged, unimpaired and young animals. Aged, impaired rats were more reactive to novelty on the hot plate test (as indicated by longer paw lick latencies); this novelty-induced pain inhibition did not habituate in aged, impaired rats following repeated plate exposures. The degree of exploratory behaviour in both the plus maze and the open field was reduced in aged, impaired rats. This effect was not entirely a consequence of deficient affective mechanisms, as measures of anxiety (e.g., time in open arms, time in inner squares) were not different among aged impaired, aged unimpaired and young animals.

These results are the first to demonstrate that behavioural deficits observed in aged, impaired animals extend beyond the impairments observed in the water maze. This behavioural profile is attributed, in part, to heightened anxiety. In addition, the impairments observed in aged, impaired animals may also reflect a reduced sensitivity to the positive incentive properties of novel stimuli.

Section snippets

Subjects

Aged, Long–Evans rats were retired breeders originally obtained from Charles River (Raleigh, NC) at nine months of age. They were housed two to three per cage (45×30×18 cm) until the time of testing (22–24 months of age). The animals were maintained on a 12:12 h light:dark schedule (lights off: 20.00) with free access to food (Purina Rat Chow) and water. Health of the animals was monitored regularly by a veterinarian, those displaying overt signs of chronic respiratory difficulties or tumours

Morris water maze

The upper panel of Fig. 1 displays the mean latencies to find the submerged platform for AI, AU and Y animals across the five days of testing in the Morris water maze. The ANOVA conducted on the latency scores yielded a significant group×days interaction, F_8,428=8.79, P<0.0001. As would be expected given the criteria used to define AI and AU animals, subsequent analyses indicated that AI animals displayed significantly longer latencies to find the platform on days two to five in comparison to

Discussion

The present results demonstrate that aged rats characterized as impaired in the Morris water maze can also be discriminated on the basis of other behavioural measures. In comparison to Y animals, AI animals consumed less of a novel milk solution, displayed a more prolonged degree of novelty-induced pain inhibition, made fewer rears, open and total arm entries in the elevated plus maze. In the open field, AI animals made fewer total square entries, reared less and engaged in non-exploratory

Are the water maze impairments related to reactivity to novelty?

The facts that AI animals were more reactive to novel stimuli and displayed deficits in habituation raise the intriguing issue of whether these deficits are related to the spatial learning and memory deficits observed in the Morris water maze. It could be argued that animals with memorial deficits would show deficits in habituation because they would be less able to recall previous stimulus exposures. Such “forgetting” would tend to maintain stimulus novelty. Whereas this hypothesis is able to

Unlinked References

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Acknowledgements

This work was supported by research grants from the Medical Research Council of Canada (MRCC)to RQ, National Institute of Aging (Grant No. AG90488) to MJM, and the Natural Sciences and Engineering Research Council of Canada to JR. RQ and JR hold Chercheur Boursier awards from le Fonds de Recherche en Santé du Québec. MJM is an MRCC Scientist. WBR is supported by a graduate fellowship from Les Fonds FCAR and a fellowship from McGill University, Faculty of Medicine (Claude J. P. Giroud Bursary in

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“Head scanning” is an investigatory behavior that has been linked to spatial exploration and the one-trial formation or strengthening of place cells in the hippocampus. Previous studies have demonstrated that a subset of aged rats with normal spatial learning performance show head scanning rates during a novel, local-global cue-mismatch manipulation that are similar to those of young rats. However, these aged rats demonstrated different patterns of expression of neural activity markers in brain regions associated with spatial learning, perhaps suggesting neural mechanisms that compensate for age-related brain changes. These prior studies did not investigate the head scanning properties of aged rats that had spatial learning impairments. The present study analyzed head scanning behavior in young, aged-unimpaired, and aged-impaired Long Evans rats. Aged-impaired rats performed the head scan behavior at a lower rate than the young rats. These results suggest that decreased attention to spatial landmarks may be a contributing factor to the spatial learning deficits shown by the aged-impaired rats.
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Measures of anxiety in behavioural tests remain largely unclear even decades after their establishment. Differences in the severity of anxiety measured by anxiety tests is an important issue that must be addressed. To test the hypothesis that the addition of light as an aversive stimulus will elicit a difference in behaviour between aged and young animals, we compared the responses of aged and young animals in the home cage emergence test (HCET) and elevated plus maze (EPM), in high aversive bright light and low aversive dim light conditions. In the HCET, our results demonstrated that young animals escaped with shorter latency and greater frequency than aged animals in both bright and dim light conditions, indicating that young animals display greater exploratory tendencies than aged animals. In the EPM, bright light conditions induced anxiogenic effects in both age groups. Interestingly, two-way ANOVA showed a significant interaction effect of age and light on the number of entries into the open arms of the EPM as well as frequency of escape in the HCET. These results show that the addition of light as an aversive stimulus in the EPM and HCET produced different responses in aged versus young animals in each test. In conclusion, significant interactions between age and light affected aged and young animals differently in the HCET and EPM, indicating that the two tests measure different aspects of anxiety.
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Citation Excerpt :
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Longitudinal human studies suggest that as we age, sociality provides protective benefits against cognitive decline. However, little is known about the underlying neural mechanisms. Rodent studies, which are ideal for studying cognition, fail to examine the independent effects of social housing while controlling for physical enrichment in all groups. In this study, rats were socially housed or nonsocially housed throughout their lifespan and tested in the radial arm maze to measure working memory (WM) and reference memory longitudinally at 3 ages. In old age, exclusively, socially housed rats made significantly less WM errors than nonsocially housed rats, while reference memory errors did not differ between groups at any age. Anxiety, as assessed behaviorally and physiologically, could not account for the observed differences in WM. These data provide the first evidence that social enrichment alone can prevent age-related WM deficits in spite of the effects of practice seen in longitudinal designs. Importantly, our model will facilitate future investigations into the mechanisms underlying the neuroprotective benefits of sociability in old age.
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In humans, memory capacities are generally affected with aging, even without any reported neurologic disorders. The mechanisms behind cognitive decline are not well understood. We studied here whether postsynaptic glutamate receptor and presynaptic vesicular glutamate transporters (VGLUTs) levels may change in the course of aging and be related to cognitive abilities using various age-impaired (AI) or age-unimpaired rat strains. Twenty-four-month-old Long-Evans (LE) rats with intact spatial memory maintained postsynaptic ionotropic glutamate receptor levels in the hippocampal-adjacent cortex similar to those of young animals. In contrast, AI rats showed significantly reduced expression of ionotropic glutamate receptor GluR2, NR2A and NR2B subunits. In AI LE rats, VGLUT1 and VGLUT2 levels were increased and negatively correlated with receptor levels as shown by principal component analysis and correlation matrices. We also investigated whether glutamatergic receptors and VGLUT levels were altered in the obesity-resistant LOU/C/Jall (LOU) rat strain which is characterized by intact memory despite aging. No difference was observed between 24-month-old LOU rats and their young counterparts. Taken together, the unaltered spatial memory performance of 24-month-old age-unimpaired LE and LOU rats suggests that intact coordination of the presynaptic and postsynaptic hippocampal-adjacent cortex glutamatergic networks may be important for successful cognitive aging. Accordingly, altered expression of presynaptic and postsynaptic glutamatergic components, such as in AI LE rats, could be considered a marker of age-related cognitive deficits.

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Reactivity to novelty in cognitively-impaired and cognitively-unimpaired aged rats and young rats

Abstract

Section snippets

Subjects

Morris water maze

Discussion

Are the water maze impairments related to reactivity to novelty?

Unlinked References

Acknowledgements

Neurobiol. Aging

Pharmac. Ther.

Neurobiol. Aging

Neuroscience

Cogn. Brain Res.

Physiol. Behav.

J. Neurosci. Meth.

Pharmac. Biochem. Behav.

Neurobiol. Aging

Working memory in aged rats

Behav. Neurosci.

Effect of handling on learning of young and aged rats

J. Gerontol.

Conditional fear-induced opiate analgesia: a competing motivational state theory of stress analgesia

Ann. N. Y. Acad. Sci.