No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Tests in Rodents for Assessing Sensorimotor Performance During Aging
Abstract
One characteristic feature of aging in all organisms is the continuous loss of adaptability to environmental perturbations. It is the result of a loss of control over the harmonization of a number of individual reactions which should be in a reciprocally interdependent state ensuring homeostasis. This chapter includes six sections which describe some sensorimotor performance tests that can be used to closely analyze age-related diminishing adaptability. The subareas which regulate and safeguard the functional systems for which the tests are models, are also presented. Procedures for measuring reflexes, muscular strength, motor activity and coordination are described by means of examples, in addition to some methods which are suitable for assessing motor behavior associated with cognitive abilities or the expression of emotional reactions. The concluding chapter discusses the possibilities and limitations of the tests for describing the scheme of stimulus-effect relationships (stimulus perception—central nervous system processing of information —responsiveness of the target organ) and stresses the need for an extensive battery of tests.
... All behavioural analysis were blinded and randomised. Righting reflex procedure was performed as previously described (26,27). The test was video documented and analysed using BORIS (Behavioural Observation Research Interactive Software, http://www.boris.unito.it) ...
Objectives: Dravet syndrome is a severe epileptic encephalopathy that begins in early childhood. More than 80% of patients with Dravet syndrome exhibit a haploinsufficiency in SCN1A, which encodes the voltage-gated sodium ion channel NaV1.1. The epilepsy is believed be caused by specific deficit of SCN1A in inhibitory interneurons of the hippocampus. However, the aetiology of other symptoms including gait disturbances, ataxia, cardiac issues and dysautonomia is less clear.
Methods: In an Scn1a knock-out (Scn1a-/-) mouse model which recapitulates clinical phenotypes, we assessed NaV1.1 and neuroinflammation throughout the central nervous system.
Results: Consistent with current understanding, wild-type expression of NaV1.1 transcript and protein were absent in knock-out mice in the prefrontal cortex, striatum, hippocampus, thalamus, and cerebellum. Increased GFAP was detected in the brain only in the hippocampus. Transcript and protein were detected in wild-type cervical, thoracic and lumbar spinal cord but not in knock-out mice. Unexpectedly, GFAP was increased in all three spinal regions. Therefore, we proceeded to perform transcriptomic analysis of cortex, hippocampus and spinal cord. Pathways associated with monooxygenase activity, fatty acid ligases and lactate transporters were highly dysregulated in the spinal cord.
Conclusion: The existence and relevance of pathology of the spinal cord in Dravet syndrome has received scant attention. Our findings are consistent with some systemic symptoms of Dravet syndrome, with the benefits of treatments which may modulate the astrocyte-neuron lactate shuttle such as Stiripentol and ketogenic dietary regimes, and with the efficacy of intrathecal delivery of therapeutics.
... Next, the PA test was performed to measure memory based on the passive avoidance of a fear-inducing context [61]. A laboratory animal learns to avoid painful stimulus by inhibiting locomotion and exploration, which is why it is also called the inhibitory avoidance test [62]. Our results showed that the SCOP group decreased in step-through latency 24 h after the acquisition trial, indicating reduced passive avoidance memory. ...
Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents. Umbelliferone (UMB) is a Apiaceae-family-derived 7-hydeoxycoumarin known for its antioxidant, anti-tumor, anticancer, anti-inflammatory, antibacterial, antimicrobial, and antidiabetic properties. However, the effects of UMB on the electrophysiological and ultrastructure morphological aspects of learning and memory are still not well-established. Thus, we investigated the effect of UMB treatment on cognitive behaviors and used organotypic hippocampal slice cultures for long-term potentiation (LTP) and the hippocampal synaptic ultrastructure. A hippocampal tissue analysis revealed that UMB attenuated a SCOP-induced blockade of field excitatory post-synaptic potential (fEPSP) activity and ameliorated the impairment of LTP by the NMDA and AMPA receptor antagonists. UMB also enhanced the hippocampal synaptic vesicle density on the synaptic ultrastructure. Furthermore, behavioral tests on male SD rats (7–8 weeks old) using the Y-maze test, passive avoidance test (PA), and Morris water maze test (MWM) showed that UMB recovered learning and memory deficits by SCOP. These cognitive improvements were in association with the enhanced expression of BDNF, TrkB, and the pCREB/CREB ratio and the suppression of acetylcholinesterase activity. The current findings indicate that UMB may be an effective neuroprotective reagent applicable for improving learning and memory against AD.
... Open field test is widely used to measure locomotor activity and anxiety-like behavior of an animal when placed in a novel environment [63,64]. Gait and arousal of all studied animals were found to be normal at all experimental time points. ...
Oxaliplatin is a widely used chemotherapeutic agent. Despite its many beneficial aspects in fighting many malignancies, it shares an aversive effect of neuropathy. Many substances have been used to limit this oxaliplatin-driven neuropathy in patients. This study evaluates the neuroprotective role of a grape pomace extract (GPE) into an oxaliplatin induced neuropathy in rats. For this reason, following the delivery of the substance into the animals prior to or simultaneously with oxaliplatin, their performance was evaluated by behavioral tests. Blood tests were also performed for the antioxidant activity of the extract, along with a histological and pathological evaluation of dorsal root ganglion (DRG) cells as the major components of the neuropathy. All behavioral tests were corrected following the use of the grape pomace. Oxidative stressors were also limited with the use of the extract. Additionally, the morphometrical analysis of the DRG cells and their immunohistochemical phenotype revealed the fidelity of the animal model and the changes into the parvalbumin and GFAP concentration indicative of the neuroprotective role of the pomace. In conclusion, the grape pomace extract with its antioxidant properties alleviates the harmful effects of the oxaliplatin induced chronic neuropathy in rats.
... Our OFT apparatus had a circle area with holes into the walls and the field marked with a grid and square crossings. The main variables recorded during the next 300 sec were: crossings (number of times the line of a square is crossed with all 4 legs), head dipping (number of putting rat's head into the hole), rearings (number of times the animal stands on its hind legs), grooming (frequency of grooming activity), number of defecation [11][12][13]. The animals were tested in the beginning of experiment before sodium nitrite injections, just after sodium nitrite injections and before stem cells injections and in 2 weeks after sodium nitrite and stem cells injections ...
Background. The last researches offer to conduct the study of Alzheimer disease (AD) mechanisms using diverse experimental models. However, it was not investigated the behavioral and cognitive impairment in rats at the different stages of vascular model of dementia of Alzheimer’s type developed by us. Subjects and methods. The experiment was performed on 32 male WAG rats weighing 180-250 g which were divided into 4 groups. Rats from group 1 and 3 were injected by aqueous solution of sodium nitrite at a dose of 50 mg/kg of body mass intraperitoneally during 14 and 28 days respectively. Groups 2 and 4 were received 500,000 mesenchymal stem cells in suspension intravenously against the background of experimental nitrite-induced AD. To estimate the behavioral reactions and cognitive functions the Open Field Test (OFT) and Passive Avoidance test (PAT) were used. Results. In all experimental groups in most cases it was found the significant decrease in vertical and horizontal activity (p <0,05) and an increase in the number of defecation in the OFT. Rats from group 3 had the drop in locomotor, research and orientation activity. In the OFT and PAT in groups 2,4 it was observed an improvement in research activity and significant cognitive functions recovery (p=0,012) after stem cell correction. Conclusions. It was found the progression of the protective inhibition and cognitive impairment during experiment. The stem cells introduction had positive effects on brain function recovery.
... CPS induced the increasing the time for escape latency and decreasing the numbers across the platform; it is shown its effect on spatial long-term memory. Another is passive avoidance test, which task is a fear-aggravated test used to evaluate learning and memory in rodent models of CNS disorders [30]. CPS also induced the latency decreased. ...
Although tooth loss is a known risk factor of cognitive function, whether and how the chewing-side preference (CSP) affects memory impairment still remains unclear. This study evaluates the behavior changes in mice after the loss of teeth on one side and explores the role of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) signal pathway within these changes. To this end, CSP mouse models with either the removal of left unilateral molars (CSP-L) or right unilateral molars (CSP-R) were established. Morris water maze test and passive avoidance test were performed to evaluate the mice's learning and memory capacity in the 4th and 8th weeks. The correlation between CSP and brain function changes was validated with changes in 5-HT and BDNF levels. CSP mice's cognitive function was found to be decreased, along with a significant decline in 5-HT1A level, especially in CSP-R mice. BDNF and TrkB levels in CSP-R mice were also significantly lowered. These findings suggest that CSP results in memory impairment, which is associated with the 5-HT-BDNF signaling pathway.
... The traction test was applied to the mice to evaluate the sedative effects of the test materials using the method described by Courvoisier with Laroche and Rousselet [21][22][23][24]. ...
Lactuca L. species belong to the Asteraceae family and these plants are traditionally used for therapeutic purposes around the world. The dried milky latex of L. serriola is known as “lettuce oil” and is used as a sedative in Turkey. This study aimed to evaluate the sedative effects and analyze the chemical compositions of latexes obtained from some Lactuca species growing in Turkey. The sedative effects were evaluated through various behavioral tests on mice. For this purpose, latexes were obtained from L. glareosa Boiss., L. viminea (L.) J. Presl and C. P, L. mulgedioides (Vis and Panćić) Boiss. and Kotschy ex. Boiss., L. saligna L., and L. serriola L. The latex from L. saligna showed the highest sedative effects, whilst L. serriola and L. viminea latexes also displayed significant sedative effects compared to the control group at a dose of 100 mg/kg. However, the latexes from L. glareosa and L. mulqedioides did not exhibit any sedative effects on mice. Characteristic sesquiterpene lactones (lactucin, lactucopicrin, 11,13β-dihydrolactucin, and 11,13β-dihydrolactucopicrin) were determined qualitatively and quantitatively by high-performance liquid chromatography (HPLC). Lactucin was identified as the main component.
Sudden changes in the environment are frequently perceived as threats and provoke defensive behavioral states. One such state is tonic immobility, a conserved defensive strategy characterized by powerful suppression of movement and motor reflexes. Tonic immobility has been associated with multiple brainstem regions, but the underlying circuit is unknown. Here, we demonstrate that a strong vibratory stimulus evokes tonic immobility in larval zebrafish defined by suppressed locomotion and sensorimotor responses. Using a circuit-breaking screen and targeted neuron ablations, we show that cerebellar granule cells and a cluster of glutamatergic ventral prepontine neurons (vPPNs) that express key stress-associated neuropeptides are critical components of the circuit that suppresses movement. The complete sensorimotor circuit transmits information from sensory ganglia through the cerebellum to vPPNs to regulate reticulospinal premotor neurons. These results show that cerebellar regulation of a neuropeptide-rich prepontine structure governs a conserved and ancestral defensive behavior that is triggered by an inescapable threat.
Adverse effects of changing climate have been associated with increase average global temperature resulting in environmental changes. We set out to investigate effects of environmental stress due to increased heat exposure on developmental milestones, behaviour, gut microbiota and neuroarchitecture in rat pups.
Pregnant Wistar rats were held in standard temperature (ST) (26±2 °C; control) or high temperature (HT) (40±2 °C) housing. After parturition, a cohort of the HT group and their pups were moved to the control/ST housing (gestational-only-exposed pup [GE]) while the other subset remained in the HT housing (gestational and postnatal exposed pups [GE+PE]). At different time points, we examined neurodevelopmental milestones and behaviour in the pups. Following sacrifice changes in gut microbiota, neuroarchitecture, cytokine levels (TNF-α, IL-4, IL-10), SOD, MDA, expression of MBP, NeUN and GFAP were determined.
We observed impaired positioning and placing of paws, prolonged righting reflex, delayed ear opening and significant decreased body weight gain in HT pups when compared with control. We identified Firmicutes and Proteobacteria and noted a significant difference in Firmicutes count between GE and GE+PE pups at P15. Furthermore, TNF-α, IL-4, IL-10 and MDA levels were increased in GE and GE+PE pups. There was also a reduction in MBP expression in the HT pups.
Taken together, our results revealed a delay in neurodevelopmental milestones in pups exposed to high HT during gestation and post natal life. Pups whose dam were exposed to high HT during gestation also showed some set back but improved over the course of testing.
Sudden changes in the sensory environment are frequently perceived as threats and may provoke defensive behavioral states. One such state is tonic immobility, a conserved defensive strategy characterized by a powerful suppression of movement and motor reflexes. Tonic immobility has been associated with multiple brainstem regions and cell types, but the underlying circuit is not known. Here, we demonstrate that a strong vibratory stimulus evokes tonic immobility in larval zebrafish defined by suppression of exploratory locomotion and sensorimotor responses. Using a circuit-breaking screen and targeted neuron ablations we show that cerebellar granule cells and a cluster of glutamatergic ventral prepontine neurons (vPPNs) that express key stress-associated neuropeptides are critical components of the circuit that suppresses movement. The complete sensorimotor circuit transmits information from primary sensory neurons through the cerebellum to vPPNs to regulate reticulospinal premotor neurons. These results show that cerebellar regulation of a neuropeptide-rich prepontine structure governs a conserved and ancestral defensive behavior that is triggered by inescapable threat.
Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã’s pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses.
The effects of stress upon emotionality, and of emotionality upon the open field activity of rats have now been studied for over four decades. Controversy remains however regarding the degree to which stress alters behavior, and the direction of that change. One reason for this is the absence of an adequate behavioral definition of stress. The present series of experiments demonstrates a standard relatively nontraumatic stress induction procedure which may be used in conjunction with open field testing. Pre-exposure to moderately intense light and white noise facilitated open field activity as measured by initial activity, lowered defecation scores, and supplementary measures (rearing, grooming, center field penetration). Further parametric, psychoendocrine, and pharmacological studies characterized the nature of the facilitation, its time course, and its modification by other manipulations. Our results suggest the initial behavioral response to stress in an open field is activation. Previous studies may have differed in their results relating stress and behavior because of subtle procedural distinctions, some of which may be identified using the present technique.
Three field experiments are reported in which skilled miniature golf players varying in age were studied in three types of activities: training, minor competitions, and large competitions. Performance (i.e., number of shots) and arousal (heart rate and subjective ratings of anxiety) measures were registered in all types of activities. The major finding was that the level of performance of older adult players deteriorated in the large competitions, whereas groups of younger adult players, junior players, and youth players performed at the same level in all three events, although all of the groups exhibited a similar increase in arousal from training and minor competitions to large competitions. We suggest that older players may have a deficit in the ability to compensate for the negative effects of nonoptimal levels of arousal because of impairments in a variety of cognitive abilities critical to successful performance.
The Handbook of the Psychology of Aging, 6e provides a comprehensive summary and evaluation of recent research on the psychological aspects of aging. The 22 chapters are organized into four divisions: Concepts, Theories, and Methods in the Psychology of Aging; Biological and Social Influences on Aging; Behavioral Processes and Aging; and Complex Behavioral Concepts and Processes in Aging. The 6th edition of the Handbook is considerably changed from the previous edition. Half of the chapters are on new topics and the remaining half are on returning subjects that are entirely new presentations by different authors of new material. Some of the exciting new topics include Contributions of Cognitive Neuroscience to Understanding Behavior and Aging, Everyday Problem Solving and Decision Making, Autobiographical Memory, and Religion and Health Late in Life. The Handbook will be of use to researchers and professional practitioners working with the aged. It is also suitable for use as a textbook for graduate and advanced undergraduate courses on the psychology of aging. The Handbook of the Psychology of Aging, Sixth Edition is part of the Handbooks on Aging series, including Handbook of the Biology of Aging and Handbook of Aging and the Social Sciences, also in their 6th editions.
Previous studies have shown that the ability of older adults to balance under conditions of reduced or conflicting sensory inputs is significantly impaired. In order to determine if sensory balance training can improve balance under these conditions two studies were conducted. In the first study healthy older adults (n = 24) were randomly assigned to a training or control group. The training group received 10 one-hour training sessions over two weeks. Training included standing with eyes open, closed, with head normal and extended backward, and on a firm surface vs on foam. Results showed significant reduction in body sway for conditions in which either ankle joint inputs alone were reduced or multiple sensory inputs were reduced (p <.006). Effects transferred to other balance tests and remained above baseline for at least 1 month after training. In a second study 12 older adults with balance deterioration related to sensory problems were given sensory training which was competency based using a protocol which was ordered from easy to difficult. Sessions were 3 times/week for 8 weeks. These subjects also showed significant improvement in balance abilities on conditions in which somatosensory inputs alone or multiple inputs were reduced. These effects were still evident 5 weeks after training ended.
The effects of increasing age on muscle fiber composition have been assessed. Cross-sections of autopsied whole vastus lateralis muscle from 43 previously physically healthy males, 15 to 83 years of age, were prepared and examined. The data obtained on muscle area, total number, size, proportion, distribution and arrangement of type 1 and type 2 fibers were analysed using multivariate regression. The ageing atrophy begins around 25 years of age and thereafter accelerates. This is caused mainly by a loss of muscle fibers, and to a lesser extent by a reduction in fiber size, mostly of the proportion of the fiber area in the muscle cross-section occupied by type 2 fibers. In the old muscles, there is a significant increase in the incidence of fiber type grouping, indicating a loss of motor neurons in the spinal cord and a reduction in the number of functioning motor units. These findings suggest a combination of a progressive denervation process and an altered physical activity level as the two major mechanisms underlying the effects of normal ageing on the human muscle.
Age-related slowing is one of the most robust findings in gerontology. Its locus is almost certainly within the central nervous system and its cause has been the thrust of much of modern geropsychology. The specific or general nature of the slowing has also received much attention both from an information processing perspective and from a neuropsychological approach. This presentation will outline a series of experiments which include information processing and kinematic motion analysis to focus on the phenomena of age-related slowing and possible explanations. The argument is made that the process of aging results in a disorganization of the central nervous system, such that quantitative (slowing) and qualitative (discoordination) changes are seen. This disorganization may be modelled using neural networks and, with respect to movement, the notion of selective disintegration of coordinative structures. If the degrees of freedom that are usually constrained to act as a unit must be independently controlled in the elderly, the cost could very well be slowness and loss of coordination.
It is generally agreed that damage to the bilateral medial temporal lobe, including the hippocampus, in man produces a severe and enduring anterograde amnesic syndrome. Leaving aside the important question of comparability of lesions in different studies, one may nevertheless ask why this most distinctive and debilitating of human memory disorders has not been found or produced in animals with hippocampal lesions. There can be only one or a combination of three possibilities: either the description of the defect in man is incomplete or inadequate, or the appropriate methods of analysis have not yet been discovered for the animal, or man and other primates are fundamentally different in the expression of brain function even though neuroanatomically the relevant regions of the brain are so very similar. This chapter will concentrate mainly on the first possibility and, by attempting then to identify points of contact between human and animal research, may show the third possibility to be less likely.
Ontogenesis is closely related to the ability to adapt to endogenous and exogenous stimuli. However, this precondition for
viability does not remain stable; it changes in correlation to the phases of life. In this long-term study with rats, the
extent to which moderate prenatal damage influences the adaptability in the juvenile, adult and senile phases was examined.
For this purpose rat fetuses were exposed to alcohol (6 g/kg bw/day) by treating the pregnant rats via drinking water from
gestation days 7 to 17. In the juvenile phase (0–3 months), no substantial differences in comparison to controls were recorded.
Exceptions were a delayed development in the negative geotaxis (posture reflex) and a transiently higher exploratory activity
in the open field test. In the adult phase (> 3–27 months), reduced performance was observed in basic functions such as body
temperature regulation. Additionally, diminished performance was seen in response to high demands in motor-coordination (rotorod).
During the senile phase (> 27 months), impairment of nearly all tested functions occurred earlier and was more pronounced.
The intention and the result of a scientific inquiry is to obtain an understanding and a control of some part of the universe. This statement implies a dualistic attitude on the part of scientists. Indeed, science does and should proceed from this dualistic basis. But even though the scientist behaves dualistically, his dualism is operational and does not necessarily imply strict dualistic metaphysics.
A larger degree of deterioration of the centrally controlled physiological, motor, and cognitive functions is characteristic of an organism's aging process. This restricted adaptation can be monitored on various organizational and functional levels. Mazes permit registration of cognitive performance in controlled motivation such as memory, spatial orientation, ability to learn, and speed of learning. The total running time is a composite parameter determined by a number of time-dependent and time-independent factors. With time-dependent factors, age-related differences remain after five repetitions, even when slight effects of training are evident. In most time-independent factors, age-related differences can be nearly eliminated by training. An example of the method “testing the limits” is to measure compensative responses under 10% normobaric hypoxia over a period of several days. Young as well as old rats reacted with the same reduction in feed intake and spontaneous activity. Adaptation to normal levels concerning motility and food consumption is accomplished less effectively and more slowly by the old rats than by the young ones. There were no differences between age groups in comparing the blood gas values of O2, CO2, and pH values. If the animals have to learn an operant conditioning schedule (fixed ratio/differential reinforcement of low rates), there are age-related divergences of performance. Under hypoxic conditions, 27-month-old animals need twice as long to reach the test criterion in the “fixed ratio” as 4- and 20-month-old rats. Only the young and middle-aged groups accomplished the task called “differential reinforcement of low rates”.
The need to assess functions such as mobility in elderly patients is increasingly recognized. Lacking other methods, clinicians may rely on the standard neuromuscular examination to evaluate mobility. Therefore, we checked the sensitivity of the neuromuscular examination for identifying mobility problems by comparing relevant neuromuscular findings with performance during four routine mobility maneuvers: (1) getting up from a chair, (2) sitting down, (3) turning while walking, and (4) raising the feet while walking. The subjects investigated were 336 elderly persons living in the community. Many subjects who performed poorly during mobility maneuvers did not have the corresponding neuromuscular abnormalities. For example, although hip and knee flexion are needed to sit down safely, abnormal hip flexion was found in only 15% and abnormal knee flexion in only 30% of the subjects who had difficulty sitting down. The relationship between neuromuscular findings and functional mobility was not predictable enough to rely on neuromuscular findings for identifying mobility problems. Therefore, a simple assessment that reproduces routine daily mobility maneuvers should be developed for use in the clinical care of elderly patients.(JAMA 1988;259:1190-1193)
A 7 x 7 foot space was marked off into 49 squares. The central square (25) contained a circular wire-mesh barrier. The animals were introduced into the field at a particular square. When food was present in the center of the field the animals made circular movements around the barrier, gradually reducing the number of movements on the edges of the field. When no food was present there was less of a tendency to circle the enclosed area and more of a tendency to explore the whole field than when food was present. The advantages of this method of observing behavior for the study of motivation are indicated. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
In order to examine the effects of efferent processes on the elicitation and modification of startle behavior, we administered
startle-eliciting stimuli to rats while they were engaged in spontaneous motor activity. When tone bursts (Experiment 1) or
electric shocks (Experiment 2) were used to elicit the reflex, its amplitude was substantially less when the rats were active
than when they were quiet. Grooming, face washing, and consuming were associated with the greatest reduction. The ability
of a 50-dB auditory prepulse to inhibit a subsequent auditory startle was also reduced during activity (Experiment 3). The
amount of inhibition produced by a prepulse was decreased even when the baseline startle responses were equated in quiet and
activity by varying the intensity of the eliciting stimulus, indicating that the reduction was not due to an artificial “floor
effect” (Experiment 4). The study demonstrated that both sensory and motor events affect reflexive responses in the rat, as
is known for the human.
Intramuscular collagen in a slow (m. soleus) and a fast (m. rectus femoris) skeletal muscle was studied by biochemical, morphometric, and immunohistochemical methods. Wistar white rats of 1, 4, 10, and 24 months were used as experimental animals. Our aim was to evaluate the effects of life-long physical training (treadmill running, 5 days a week for 1, 3, 9, and 23 months depending on the age attained). The biochemical concentration of collagen was higher in m. soleus than in m. rectus femoris and it increased in youth and in old age in m. soleus. The trained rats had higher concentrations of collagen than the untrained rats at 10 and 24 months. The morphometrically measured area-fractions of both the endomysium and perimysium were higher in m. soleus than in m. rectus femoris. The age-related increase in intramuscular connective tissue was of endomysial origin. The immunohistochemical staining of type-I, -III, and -IV collagens indicated the more collagenous nature of m. soleus as compared with m. rectus femoris for all major collagen types; this was most marked for type-IV collagen of basement membrane. The results indicate that both age and endurance-type physical training further distinguish the slow and fast muscles with respect to their connective tissue.
To investigate whether an elevated plus-maze consisting of two open and two closed arms could be used as a model of anxiety in the mouse, NIH Swiss mice were tested in the apparatus immediately after a holeboard test. Factor analysis of data from undrugged animals tested in the holeboard and plus-maze yielded three orthogonal factors interpreted as assessing anxiety, directed exploration and locomotion. Anxiolytic drugs (chlordiazepoxide, sodium pentobarbital and ethanol) increased the proportion of time spent on the open arms, and anxiogenic drugs (FG 7142, caffeine and picrotoxin) reduced this measure. Amphetamine and imipramine failed to alter the indices of anxiety. The anxiolytic effect of chlordiazepoxide was reduced in mice that had previously experienced the plus-maze in an undrugged state. Testing animals in the holeboard immediately before the plus-maze test significantly elevated both the percentage of time spent on the open arms and the total number of arm entries, but did not affect the behavioral response to chlordiazepoxide. The plus-maze appears to be a useful test with which to investigate both anxiolytic and anxiogenic agents.
The purpose of this paper is to demonstrate that rats can rapidly learn to locate an object that they can never see, hear, or smell provided it remains in a fixed spatial location relative to distal room cues. Four groups of rats were permitted to escape from opaque water onto a platform which was either just above or just below the water surface, and in either a fixed or varied location. Learning occurred rapidly except for the group for whom the escape platform was below the water surface and moved about from place to place. Transfer tests revealed that a spatial location search strategy was employed by the group for whom the platform was below water but in a fixed location. A second experiment investigated this learning further, revealing instantaneous transfer when the rats were required to approach the platform from a novel starting position. The data of both studies are discussed in relation to recent work on spatial memory in the rat. The concept of the “acuity” of spatial memory is introduced and the procedures used may provide a new approach to comparing spatial memory with classical and instrumental conditioning.
In a lifespan study, measures of motor behavior and somatic growth were recorded monthly from 31 male and 31 female gerbils. Each month, after measures were recorded, the gerbils were placed in a large, outdoor environment, or in a small indoor control cage for one hour. The enrichment experience for one hour a month had no effect on motor behavior between 2 and 7 months of age, but facilitated adolescent development. Area of the ventral gland increased more rapidly in gerbils given environmental enrichment. In male gerbils, the hindlimb was longer in those given environmental enrichment, but the opppsite was true in female gerbils. More female gerbils and seizures than did male gerbils after 3 months of age, and enrichment had no significant effect on seizures in female gerbils. In male gerbils, however, more of the gerbils given enrichment experience had seizures from 2 to 4 months of age and fewer had seizures at 5 and 6 months of age than did controls.
When placed in a tank of water, aged rats (24 to 27 months old) showed marked impairments in swimming. Compared with young
adult rats (3 to 4 months old), the older animals moved their limbs less vigorously and were less successful in keeping their
heads above water. The young, but not old, rats maintained a position nearly horizontal to the water surface and planed across
it. These movement dysfunctions of aged rats resemble those seen in young adult animals that have sustained injury to brain
dopamine-containing neurons. The swimming impairments of the aged rats were reversed by the dopamine receptor stimulant apomorphine
and by the biosynthetic precursor of dopamine, L-dopa. Thus, age-related alterations in brain dopaminergic systems may be
responsible for some of the movement disturbances associated with senescence.
A method to determine age related changes in the neuromuscular competence of mice is described. When young animals are placed on a tightrope, they are able to grasp the string with the four legs and tail and move to reach a side pole. Usually, young obese and senescent mice cannot lift their hind legs and, after hanging for a few seconds from the forepaws, they fall on the cage bedding placed underneath. The mice are scored positive if they reach the side pole in 60 s or less.When the results are expressed as Transported biomass (total weight of the mice scored positive/number of mice tested, including those which failed the test) the age related vitality loss of a mouse population can be revealed before this loss is manifested in a high mortality rate.This simple determination of neuromuscular coordination and vigor has demonstrated its usefulness in studies from our laboratory on the rate of aging of mice treated with antioxidants.
In laboratory rats (Rattus norvegicus) aged 1 to 21 days emergence of postural and locomotor skills was studied in the open field and in experimental situations with homing used as motivation. Righting is mediated initially by curving and rocking of the trunk, later head and shoulder are rotated, and lastly the hindlimbs turn and provide co-ordinated support. Pivoting prodominates during the second half of the first week, crawling during most of the second week, and walking or running by the end of the second week. Balancing on narrow paths and compensating for lateral displacement on rotating rods mature later, as do various skills (climbing up or down on inclined surfaces, rods and ropes, and jumping across gaps) that require substantial hindlimb co-ordiantion.
The sweating responses to thermal stimulation and to the intradermal injection of acetyl choline or methacholine were measured
in 28 men and 18 women aged 70 and over and were compared with the responses in young control subjects of both sexes. There
was found to be a marked reduction in the sweating activity of the majority of aged men in comparison with the younger age
groups and the body temperature threshold for the onset of sweating was increased. The reduced response and elevated threshold
were even more pronounced in aged females. There is considerable variability in response in different subjects and at different
bodily sites. Impairment of thermoregulatory function due to diminished or absent sweating is thought to be one of the factors
responsible for increased mortality in die elderly population during heat-waves
A mechanomyographic response of the hind foot to passive straightening and bending, as well as an electromyographic activity of the gastrocnemius and tibialis anterior muscles were recorded in old (35-44-month-old) and young female rats. In old rats, spontaneous, tonic electromyographic activity patterns were concurrently observed in both antagonistic muscles; they were low-amplitude, dense tonic activity and continuous, high-amplitude, sparse electromyographic activity. The tonic electromyographic activity was correlated with a decline in the strength and mass of muscles, as well as with motor disturbances, including paresis of the rigidly straightened backward hind legs, dragged behind by an animal. In muscles of old rats, morphological features of a chronic denervation atrophy were found. Baclofen (10 and 15 mg/kg, i.p.) diminished the spontaneous tonic electromyographic activity and potently decreased the whole body muscle tone, whereas Madopar (50 mg/kg of L-DOPA+12.5 mg/kg of benerazide) was ineffective. It is suggested that old rats in which the above-described pathologic alterations are observed might be a useful animal model in the search for basic etiopathological mechanisms of spasticity and similar disturbances found in humans.
We previously reported that the freely moving male Fischer-344 rat provides a useful model to demonstrate the progressive impairment of eyeblink conditioning associated with aging. However, because the youngest F-344 rats only performed at 60% of maximum, we ran the same experiment with hybrid rats and discovered most (i.e., those age 9-24 months) learned rapidly and exhibited conditioned responses on greater than 80% of trials by the end of two training sessions. In contrast, the aged rats (36 months) exhibited significantly fewer CRs on all four training days. However, unlike all ages of F-344 rats (3-30 months) which were run in our last study, these aged hybrid rats exhibited considerable improvement with extra training. These data indicate clear differences in the rate of learning between the two strains and suggest that even young F-344 rats may have deficits in the neural circuits which mediate eyeblink conditioning. Other anecdotal findings on differences between the two strains are noted.
In young adults rats (5-month-old) d-amphetamine (2 mg/kg/d), administered on a long-term basis via drinking water, caused a moderate reduction in the intake of nutriments, which in part normalized within three weeks. Self-administration of a daily dose of 20 mg per kg diazepam over a period of 26 days led neither to hypodipsia nor to anorexia. Pentylenetetrazol (70 mg/kg/d) primarily produced a hypodipsia. The three drugs did not influence body weight. In 27-month-old rats d-amphetamine and pentylenetetrazol had the same qualitative effects. Intake of nutriments and the development of body weight were influenced more strongly than in young rats. Diazepam also had a marked effect in old animals. Nootropics (piracetam, pyrithinol, hydergin, centrophenoxin, aniracetam) had no effects on the parameters observed. When the agents were given in combination in both age groups the nootropic piracetam (230 mg/kg/d) weakened the effects induced by d-amphetamine, pentylenetetrazol or diazepam alone. The benzodiazepine, however, enhanced the loss of body weight and fluid intake in old rats caused by the stimulant or analeptic, whereas food intake remained unaffected. The results support the hypothesis that an organism's adaptivity to external and internal stimuli is reduced in later life. The behavior of young and old rats in the open field was not affected by any drug medication.
Rodents have proven to be a useful general model for aging research. Although they are not necessarily appropriate for the study of such specific human age-associated diseases as atherosclerosis, rodents have provided the basis for important age-related findings in many diverse areas, including nutrition, behavior, immunology, physiology, oncology, biochemistry, and neurobiology. Contributions in these areas are briefly reviewed.
Stimuli consistently paired with shock become capable of suppressing ongoing operant or consummatory behavior (the conditioned emotional response--CER) or elevating the amplitude of the startle reflex (fear-potentiated startle). These changes are used to infer a central state of fear which involves the central nucleus of the amygdala and its efferent projections to the brainstem. The present paper reviews how psychoactive drugs affect these measures. Both the CER and fear-potentiated startle are reduced by benzodiazepines, barbiturates and opiates. Advantages and disadvantages of these animal tests of anxiety are discussed.
The mammalian behavioral antipredator defense systems have been characterized in terms of reactions to present, localizable, threat stimuli: Analysis of the relationship between features of the predator and the environment, and specific defensive behaviors indicates that the latter can be predicted with a high degree of accuracy. A different set of defensive behaviors are seen when rats living in burrow systems are confronted by a predator outside the burrow. Flight to the burrow and immobility inside the burrow are followed by active investigation of the surface where the cat was seen (risk assessment), with all of these accompanied by inhibition of nondefensive behaviors such as eating, drinking, sexual behavior and aggression. Two additional behaviors are described in this context, ultrasonic cries made at a high initial rate (50% time) by animals inside the burrow systems, and declining over 1-2 hours following predator exposure, and, a specific modification of eating patterns when the subjects return to the surface and begin to eat. Eating bouts are shortened, with fewer episodes of continuous eating, interspersed with intervals of scanning of the environment, a vigilance activity previously reported in field research. This analysis of a broad spectrum of defensive behaviors is being used to develop test batteries providing simplified models of these phenomena.
The interaction effects between adult aging and incremental levels of movement complexity were studied in young, middle-aged,
and older healthy females. Utilizing a two-choice reaction time (RT) paradigm, movement complexity as a factor of response
programming was varied in a microswitch pressing task by altering the number of sides of the body and the number of fingers
controlled. The speed of response programming was found to be age dependent and to interact with movement complexity across
age groups. The results confirmed that as movement complexity increases, the effects of adult aging on RT increase. This study
further emphasizes the robustness of the movement complexity x age effect, in that older individuals were found to be much
more sensitive to small changes in movement complexity than younger subjects. The comparison results of three adult age groups
suggested this sensitivity to movement complexity is progressive over the adult life span
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.
The goal of this experiment was to determine the correlations among different behavioral and neurobiological measures in aged rats. Aged Sprague-Dawley rats were given a battery of cognitive and sensorimotor tests, followed by electrophysiological assessment of sleep and biochemical measurements of various neurotransmitter systems. The behavioral tests included the following: Activity level in an open field; short-term and long-term memory of a spatial environment as assessed by habituation: spatial navigation, discrimination reversal, and cue learning in the Morris water pool; spatial memory in a T-maze motivated by escape from water; spatial memory and reversal on the Barnes circular platform task; passive avoidance; motor skills. Sleep was assessed by electrographic cortical records. The following neurotransmitter markers were examined: Choline acetyltransferase; the density of nicotinic, benzodiazepine and glutamine receptors in the cortex and caudate nucleus; endogenous levels of norepinephrine, dopamine, and serotonin in the cortex and hippocampus. The duration of bouts of paradoxical sleep was strongly correlated with several cognitive measures and selected serotonergic markers. This finding suggests that changes in sleep patterns and brain biochemistry contribute directly to deficits in learning and memory, or that the same neurobiological defect contributes to age-related impairments in sleep and in learning and memory.
These studies were designed to assess whether aged rats have a similar degree of impairment across a number of behavioral tasks. In Experiment 1, no relationship between the severity of a spatial learning impairment and reaction time performance was found among aged rats. This result is in contrast with a relationship that was found in aged rats between spatial learning and the rate of recovery from gustatory neophobia (results of Experiments 2 and 3). Experiment 3 further showed that the relative spatial learning abilities of two subgroups of aged rats, i.e., "impaired" and "unimpaired," were related to transfer training in the water maze conducted six weeks after the completion of original training. The subgroups of aged animals were also distinguished by their latencies (but not errors) on a circular holeboard maze, and the pattern of water consumption during the light/dark cycle determined at the end of the entire protocol (13th week of testing). Other measures, however, did not distinguish the aged subgroups that were formed on the basis of spatial learning ability.
1. In wild and laboratory rats, offense and defense constitute nonoverlapping behavior patterns seen in response to resource or dominance challenge, or, to predatory, conspecific or environmental threat, respectively. 2. Defensive behaviors are determined by both the threat stimulus and the situation. Defense patterns to discrete, approaching, predators or conspecifics and to nondiscrete, potential, threat have several behaviors in common. However, the latter also includes an important risk assessment complex not seen to discrete, present, threat. Behaviorally and functionally, risk assessment shows considerable similarity to the apprehensive expectation and vigilance and scanning components of generalized anxiety reactions. 3. There are parallels between lower mammal offense and human angry aggression in terms of eliciting stimuli, and a variety of experiential factors including inhibition by fear/pain, and reinforcement effects. 4. A variety of neuroanatomical or pharmacological manipulations have different, often opposite, effects on offense and defense. Differentiation of the two and attention to the specific behaviors involved provide a more precise basis for the use of these patterns as animal models of emotion states.
Animal models for the study of anxiolytic agents are reviewed and evaluated according to pharmacological and behavioral criteria. Although there are important exceptions, in general, most early animal models have not provided a reliable basis for identifying compounds with potential anxiolytic action, or for delineating the mechanisms of anxiolytic drug action. The possibility that phylogenetically 'prepared' forms of defensive learning might serve as a basis for the study of anxiolytic agents is introduced.
Rats that are placed in a novel environment containing a probe will explore the environment and the probe. Exploration of the probe is reduced when the probe is electrified. We here report that chlordiazepoxide blocks this inhibition, and have determined some of the pharmacological features of this new experimental procedure. The procedure appears to be sensitive to the effects of several benzodiazepines, barbiturates, and related compounds. Limited activity was observed with most 5-HT antagonists, ritanserin, an anticholinergic, a beta-adrenergic blocker and a neuroleptic. Of the antidepressants, only imipramine had some limited activity. Inactive compounds in this procedure include benzodiazepine antagonists, buspirone, convulsants, opiates, an opiate antagonist, stimulants, a putative DA agonist and antagonist, histamine antagonists, a cholinomimetic, anticholinergics, a NE antagonist, alpha 2 agonists, an alpha 2 antagonist, MAO inhibitors, 5-HTP and LSD.
The goals of this research were to develop a within-subject test of spatial working memory and performance for the rat in a T-maze, based on a delayed alternation, or "win-shift" foraging strategy. Using this model, specific aims were to compare the effects of: (1) age, (2) basal forebrain, medial septal, and amygdala lesions, (3) four vessel occlusion (4-VO), forebrain ischemia, and (4) physostigmine, scopolamine, arecoline, piracetam, and clonidine on memory and performance of young middle-aged, and old rats. Aging significantly impaired working memory and performance of Long-Evans rats. Memory of septal and basal forebrain, but not of amygdala lesioned rats was significantly impaired without effects on performance. Transient, 4-VO forebrain ischemia produced significant memory impairment, without effects on performance, and highly selective CA1 cell loss in the hippocampus. Physostigmine enhanced working memory in middle-aged and old rats. Scopolamine impaired memory in young, middle-aged, and old rats. Physostigmine reversed the scopolamine impairments of working memory. Arecoline enhanced memory in old rats without effects on performance. Piracetam and clonidine had no direct effects on memory, but piracetam increased and clonidine decreased speed of performance. From the aging, lesion, ischemia, and drug studies it was concluded that there was a convergence of evidence from 4 different approaches for a critical role for the hippocampus, particularly the CA1 fields, in spatial working memory.
Studies are reviewed which indicate that hippocampal frequency potentiation (the growth of neural responses during repetitive synaptic stimulation) is impaired in aged rats, and that this impairment may be important in learning and memory deficits found in these aged animals. Intracellular recording and ultrastructural studies suggest that both hippocampal frequency potentiation and the age deficit in such potentiation are synaptic processes (probably presynaptic), and that the deficit may be due to an age-related increase in calcium influx during depolarization. The latter could in some way result from alterations in the function of a Ca-mediated inactivation of Ca current mechanism recently found in hippocampal neurons. Since major hippocampal changes occur with aging in both rodents and humans, it seems possible that these data are also relevant to human brain aging. Consequently, it is suggested that Alzheimer's disease results from an acceleration of normal age-related neuronal calcium conductance changes by some unknown process (e.g., viruses, aluminum, genetic factors, etc.), leading to a rapid deterioration of brain structure.
Evidence for age-related changes in spatial memory in rodents and humans is presented, along with data that suggest that the hippocampal formation is necessary for normal performance on spatial tasks in both species. An examination of the electrophysiological characteristics of this structure in rats suggests that the changes that occur with age in the hippocampus are selective, but that at least two primary types of alterations contribute to the spatial cognitive impairment seen in these animals. These include a deficit in the ability to maintain synaptic enhancement and a reduction in the accuracy of information processing ability of single hippocampal neurons.
This paper reports a series of experiments that assessed learning and memory performance in aged rats from a neuropsychological perspective. Relative to young adults, old rats displayed rapid rates of forgetting, increased susceptibility to interference, and poor long-term recall of specific experiences. There were no age differences on tests of short-term memory. In general, the performance of aged rats paralleled that of young rats with restricted lesions to the hippocampus, thereby supporting the conclusion that normal memory loss with age is related to progressive hippocampal dysfunction.
Research is reviewed concerning the age-related learning deficit observed in a 14-unit T-maze (Stone maze). Rats and mice of several strains representing different adult age groups are first trained to criterion in one-way active avoidance in a straight runway. Then training in the Stone maze is conducted which involves negotiation of five maze segments to avoid footshock. Results indicate a robust age-related impairment in acquisition observed in males and females, and in outbred, inbred, and hybrid strains. Pharmacological studies using the muscarinic antagonist, scopolamine, in young and aged rats indicate cholinergic involvement for accurate encoding during acquisition of this task. Retention aspects of storage and retrieval do not appear to be affected by scopolamine treatment. Bilateral electrolytic lesions to the fimbria-fornix of young rats also produce an acquisition deficit to implicate involvement of the septo-hippocampal cholinergic system in Stone maze learning. A salient feature of Stone maze performance is the tendency to demonstrate an alternation strategy in solving the maze. This strategy is exacerbated by impairment of cholinergic neurotransmission with either scopolamine treatment or fimbria-fornix lesions. Various models of hippocampal function are applied toward the psychological characterization of the Stone maze task without complete success. Future research is outlined to provide more thorough psychological characterization of maze performance, to analyze the specificity of cholinergic involvement in the task, and to test possible therapeutic interventions for alleviating the age-related impairments observed.
One of the several sources of interest in aging animal brains is their potential as models of the aging human brain. In this review we examine whether neuron numbers and sizes change similarly in aging human, monkey and rodent brain regions which data are available from more than one species. The number of brain regions studied in more than one species is surprisingly limited. Some regions show correspondence in age-related changes between humans and selected animal models (primary visual cortex, CA1 of hippocampus). For the majority of regions the data are conflicting, even within one species (e.g., somatosensory cortex, frontal cortex, cerebellum, cholinergic forebrain areas, locus coeruleus). Although some of the conflicting data may be attributed to procedural differences, particularly when data are expressed as density changes, much must be attributed to real species and/or strain differences in rodents. We conclude that neuron numbers and sizes may show similar age-related changes in human and animal brains only for sharply defined brain regions, animal species and/or strains, and age ranges.
A functional decline in the hippocampal formation may underlie the emergence of spatial learning deficits in aged rodents. In this study, sodium-dependent high-affinity choline uptake (HACU) was used to monitor hippocampal function in response to training on a spatial task. The subjects were male Long-Evans rats at either 4 months or 22-24 months of age. Animals were trained to locate a camouflaged escape platform in the Morris water maze. Each animal that received place training had a yoked counterpart that was exposed to swimming in the maze but was not required to learn the task. Animals, both young and aged, were sacrificed after attaining a criterion performance. Relative to animals in the yoked condition, place training significantly reduced HACU in both the young rats and in a subpopulation of the aged animals that learned the task rapidly. In contrast, for aged rats that had an impaired rate of acquisition, no effect of place training on HACU was observed. These results provide evidence for a relationship between the behavioral capacities of aged rats and changes in the status of hippocampal function.
Three pairings of rats (two derived from divergent, selective breeding and one from divergent environmental conditions) were compared with regard to behavioral and hormonal parameters. Striking differences were observed: results obtained in our own laboratory as well as those found in a review of the literature pointed to higher emotionality (e.g., increased defecation and corticosterone secretion, etc.) in Roman low-avoidance, Wistar-Kyoto and group-housed rats, as compared to their respective counterparts, Roman high-avoidance, spontaneously hypertensive, and individually housed Wistar rats. Concomitant receptor binding studies reviewed here (3H-diazepam- and 3H-imipramine-binding sites) have revealed, however, less consistent intrapair differences.