A behavioral study of temporal processing and visual persistence in young and aged rats.

Young rats were presented with light flash prepulses varying in duration from 1 to 128 msec, with light offset or light onset fixed at 70 msec prior to an acoustic startle stimulus (Experiment 1A), and, with single or paired 1-msec flashes, the 2nd (or only) flash given 100 to 500 msec before the startle, and 1 msec to 400 msec interflash intervals (Experiment 1B). Older rats (10 and 20 mo old) received the same single and double flashes but with the maximum interflash interval extended to 1,500 msec (Experiment 2). Reflex inhibition increased with increased duration from 1 to 8 msec and decreased as light onset progressively exceeded 100 msec. Inhibition for both single and double flashes also declined for onset lead times beyond 100 msec, then increased for a double flash once the interflash interval exceeded 100 msec in young and middle-aged rats and 1,500 msec in the oldest rats. Peak inhibition was much reduced in the oldest rats at short lead times but was greater than that of younger rats at long lead times. These data suggest that aged rats process visual stimuli more slowly than younger rats and show poorer temporal acuity coupled with greater visual persistence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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

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 degrees 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.     

Partial hippocampal inactivation: Effects on spatial memory performance in aged and young rats.

Changes in anatomical or functional connectivity during normal aging are thought to contribute to cognitive alterations over the lifespan. Neural network theories predict that synaptic loss in an aging brain could place the organism near the point of dysfunction in the nonlinear curve defining neural compromise versus performance. The present experiments examined whether aged rats are closer to this point of behavioral dysfunction by reversibly inactivating one or both hippocampal hemispheres. As expected, bilateral tetracaine inactivation of the hippocampus disrupted spatial memory in both age groups. Unilateral left hippocampal inactivation significantly increased errors only in aged rats; however, unilateral inactivation of the right hippocampus had no effect. The present outcome could reflect more extensive synaptic dysfunction in the aged right hippocampus or a greater involvement of the left hippocampus in spatial working memory problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stress and neurosteroids in adult and aged rats

The progesterone derivative 3 alpha-hydroxy-5 alpha-pregnan-20 one (allopregnanolone/AP) and the deoxycorticosterone derivative 3 alpha-21-dihydroxy-5 alpha- pregnan-20 one (allotetra-hydrodeoxycorticosterone/THDOC) are endogenous neuroactive steroids endowed with neuromodulatory actions in the central nervous system. Their best-characterized membrane-receptor-dependent action consists in the amplification of GABA-gated chloride currents mediated by specific interactions with the GABAA receptor complex, which appears responsible for the pharmacological effects (anxiolytic, anticonvulsant, hypnotic/anaesthetic) of exogenously administered AP and THDOC. Several acute stress paradigms and different negative allosteric modulators (isoniazid and FG 7142) of GABAA receptors time dependently increase brain and plasma concentrations of AP and THDOC only in intact or sham-operated but not in adrenalectomized-orchiectomized rats. These results suggest that acute stress and inhibitors of GABAA receptors increase the brain and plasma neurosteroid concentrations via a reduction of the inhibitory action exerted by GABA on the hypothalamic-pituitary-adrenal axis. The comparison between the time course of the changes in GABAA receptor function and of their behavioral correlates (proconflict behavior) and that of the changes of endogenous neuroactive steroids are consistent with the view that AP and THDOC may play a role in restoring the GABAergic tone to prestress conditions, by limiting the duration and the extent of its stress-induced reduction. The acute stress-elicited increase of AP and THDOC is observed in adult as well as in aged rats, which show a reduced basal GABAergic transmission and a greater response to the effect of stress in terms of their brain cortical neuroactive steroid concentrations than adult rats.     

Tyrosine hydroxylase- and nitric oxide synthase-immunoreactive nerve fibers in mitral valve of young adult and aged Fischer 344 rats

Using confocal fluorescence microscopy we studied, in whole mounts of heart mitral valves of young adult and aged Fischer 344 rats, the distribution of nerves containing the catecholamine marker tyrosine hydroxylase (TH) or the synthetic enzyme marker for nitric oxide, nitric oxide synthase (NOS). TH-IR was localized in two separate nerve plexuses which do not intermingle. The 'major' plexus arose from the annulus region, traversed the basal zone of the valve, and ramified in the intermediate zone to form a dense network of fine fibers. The 'minor' plexus was restricted to the distal zone and originated from bundles that ascended the chordae tendineae to enter the valve cusp. A concentric zone located between the major and minor plexuses was devoid of TH-IR nerve fibers. Both plexuses demonstrated (i) nerves that contained numerous varicosities along the length of each fiber, (ii) many terminal axons and (iii) different shaped terminal axon endings. With age, the density of TH-IR innervation in the mitral valve was markedly reduced; and nerve fibers of the minor plexus were limited to the chordae tendinae, without extending into the valve cusp itself. NOS-IR fibers in the mitral valve formed a loose network that extended from the annulus to more than halfway down the cusp. The varicose beads of the terminal NOS-IR axons appeared to become progressively smaller and less intensely fluorescent until they disappeared at the terminal endings, which showed no specializations. No NOS-IR fibers were observed in the distal zone of the valve leaflet or in the chordae. In the aged mitral valve, the density of NOS-IR nerves was decreased, as compared with NOS-IR innervation in the young adult valve. The existence of TH and NOS as well as other signal molecule markers in heart valve nerves and the disparate patterns of their distribution and localization provide evidence supporting the theory that heart valve nerves form a complex reflexogenic control system in the mitral heart valve. In summary, two distinct neural architectures are described for TH-IR and NOS-IR valve nerves, respectively. The former are believed to be axons dedicated to sympathetic motor functions. The NOS-IR valve nerves may have sensory and/or postganglionic parasympathetic motor functions. An implication of these findings is that different, but perhaps related, valve functions may be mediated by separate, dedicated circuits.     

Taste aversion learning in young and adult rats.

Compared a total of 159 male Long-Evans rat pups and adults on their ability to learn taste aversions with 1- and 2-bottle tests, 2 different illness-inducing agents and flavors, and varying taste–illness delays. Rat pups learned taste aversions with either 1- or 2-bottle tests, but only with short taste–illness delays. Delays of 60 min were sufficient to block taste aversion learning in pups. Pups also failed to demonstrate neophobia to a novel taste. These findings suggest that pups forget taste information more rapidly than adults, perhaps because taste information is not so salient for pups as for adults. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensory preconditioning effects in young and adult rats.

Compared 64 90- and 64 25-day-old hooded rats on a test of sensory preconditioning (spc). Initially, 2 paired stimuli (s1, s2) were presented, following which s2 was paired with shock. The effects of s1 on 3 measures of lick-rate suppression were taken as indices of spc, these being: standard suppression ratio, lick latency following stimulus onset, and lick latency following stimulus offset. Results are as follows: (a) an spc effect was not demonstrated by the standard suppression ratio, and these data are explained by reference to possible habituation mechanisms or preexposure effects; (b) young ss but not adults showed an spc effect using onset latency; and (c) the reverse held true for the offset latency measure. These latter 2 findings are discussed in terms of differences in associative and discriminative capacities between young and adult ss. (french summary) (19 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proactive interference effects on short-term memory in rats: II. Effects in young and aged rats.

Whether the short-term memory impairments of aged rats in an operant delayed-matching task is attributable to increased susceptibility to proactive interference (PI) was tested. Groups of young and aged rats were trained on the task, and the previously reported delay-dependent deficit of aged rats was replicated. The aged rats showed a significantly greater decline in performance on previous-response-opposite trials compared with previous-response-same trials than did young rats, when tested over the same range of delay intervals, suggesting a higher sensitivity to PI. However, this effect was established against a higher overall baseline performance of the young animals on both types of trials. When the young and aged animals were equated for performance on previous-response-same trials (by increasing the range of delay intervals used for testing the young animals), the interaction effect was abolished. Thus, the delay-dependent deficits of aged rats are independent of their sensitivity to PI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Myocardial injury after hypoxia in immature, adult and aged rats

We evaluated the abilities of isolated perfused hearts from immature (IM) (2.5-3 months), ADULT (11-13 months) and OLD (24-26 months) Fischer 344 rats to tolerate and recover from oxygen deprivation. Hearts were perfused at 60 mmHg for a 30-minute prehypoxic period with oxygenated buffer supplemented with 10 mM glucose (+insulin) and 2 mM acetate, then 30 minutes with substrate-free, hypoxic buffer gassed with 95% N2:5% CO2, and finally reoxygenated for an additional 45 minutes with the same buffer used during the prehypoxic period. During prehypoxia, all groups were similar in ventricular mechanical function, glycogen content, high-energy phosphates (HEP), reduced glutathione (GSH), Ca+2 content, and mitochondrial state 3 rates. At the end of the hypoxic period, glycogen levels were similar and almost completely depleted in all groups, HEP were lower (p < 0.05) in ADULT vs other groups, mitochondrial state 3 rates were decreased (24%, p < 0.05) only in ADULT, and GSH was depleted by 34% in IM vs only 13% in OLD (p < 0.05). After 45 minutes of reoxygenation, IM and OLD had recovered 48% and 45% of their respective prehypoxic function which was two-fold greater than the 23% recovery by ADULT. Loss of cytosolic enzymes, an indicator of sarcolemmal damage, was estimated by measuring lactate dehydrogenase (LDH) release. LDH release and Ca+2 content during reoxygenation in IM were only about half of that observed in ADULT or OLD. We conclude that immature and aged hearts tolerate and recover from hypoxia better than hearts from adults, and that the sarcolemmal membranes of immature rat hearts are less susceptible to damage from hypoxic stress than those of either older group.     

Daily variation in the urinary excretion of furosemide in young and aged rats

We have recently demonstrated that the time-dependent difference in urinary excretion of furosemide, a loop diuretic, diminishes during the aging process and disappears by 18 months of age in rats. The present study was undertaken to examine whether the amplitude of the daily variations in the urinary excretion of furosemide or their pattern, or both, are influenced in aged animals. Young (3 months of age) and aged (30 months of age) Wistar rats were maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Furosemide (30 mg/kg) was given orally at 4 am, 8 am, 12 am, 4 pm, 8 pm or 12 pm. Urine was collected for 8 hours after furosemide administration and urinary excretion of furosemide was determined. There were significant daily variations in the urinary furosemide and the urine volume with the peak at 8 am and the trough at 12 pm in both groups of rats. The differences in these parameters between the 8 am and 12 pm trials were significantly smaller in the aged than in the young rats. These results suggest that the age-related alteration in the time-dependent phenomenon of furosemide is caused by the decreased amplitude of the daily variation in the urinary furosemide excretion and its diuretic effect.     

Effects of punishing active avoidance in young and adult rats.

Examined whether age-related differences in suppression occur when a learned response is punished. 8 groups of weanling and adult male Holtzman rats (N = 96) received active-avoidance training and subsequent punishment for that response. Following active avoidance, Ss were assigned to a regular extinction group or to 1 of 3 punishment-delay (0-, 2-, or 10-sec.) groups, which received shock in the goal box. Although weanlings and adults were equivalent in active-avoidance acquisition, under the immediate punishment condition immature Ss required significantly more trials to learn passive avoidance. A delay-of-punishment gradient was obtained in adults but not in weanlings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus control of shuttle avoidance in young and adult rats.

Investigated stimulus generalization of 2-way active avoidance behavior in young and adult rats. In Exp. I with 12 adult and 12 young male Holtzman albino rats, CS frequency gained marked and comparable control over responding in both age groups; variation of background frequency prior to a no-tone CS, however, failed to exert any substantial control over avoidance behavior in either age group. In Exp. II with 12 Ss, Pavlovian frequency discrimination training was interpolated between acquisition of the shuttle response and generalization testing. Relative to their respective single stimulus control groups, the adult Ss showed a reliable peak shift in modal responding and the young Ss revealed a distortion in the gradient at frequency values on the side of CS+, opposite that of CS-. Although the occurrence of a peak shift was somewhat surprising in light of the fact that CS- here served as a "safety" signal, the data are interpreted as consistent with explanations of discrimination learning based upon the summation of excitatory and inhibitory gradients. In general, both experiments suggest that variations of CS frequency in an active avoidance situation tends to result in similar gradients for both young and adult Ss. The disparity between the present and previous findings are discussed in terms of the response requirements of the test situation. (French summary) (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preventing and alleviating hypothermia-induced amnesia in weanling and young adult rats.

Reminder (Experiment 1) and familiarization (Experiment 2) treatments were found to have similiar effects on the 24-hr retention performance of 24- to 26- and 90- to 100-day-old rats that either did or did not undergo an amnesic treatment (hypothermia) immediately after training. Similar degrees of retrograde amnesia and normal forgetting were evident in both trained age groups that were not subjected to familiarization or reminder treatments. These results suggest that memory processes in weanling and adult rats are similar in susceptibility to disruption by an established amnesic treatment (hypothermia) and in the ease of prevention of and recovery from amnesia by recognized preventive (familiarization) and alleviation (reminder) measures. The similarity of the effects of these preventive and alleviation treatments on normal forgetting and induced amnesia suggests that experimentally induced amnesia may be a fruitful approach to studying the ontogeny of memory processes and, more specifically, to studying factors that influence infantile amnesia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Single soleus muscle fiber function after hindlimb unweighting in adult and aged rats

This investigation compared how hindlimb unweighting (HU) affected the contractile function of single soleus muscle fibers from 12- and 30-mo-old Fischer 344 Brown Norway F1 Hybrid rats. After 1 wk of HU, functional properties of single permeabilized fibers were studied, and, subsequently, the fiber type was established by myosin heavy chain (MHC) analysis. After HU, the relative mass of soleus declined by 12 and 19% and the relative mass of the gastrocnemius declined by 15 and 13% in 12- and 30-mo-old animals, respectively. In 12-mo-old animals, the peak active force (5.0 +/- 0.2 x10(-4) vs. 3.8 +/- 0.2 x10(-4) N) and the peak specific tension (92 +/- 4 vs. 78 +/- 3 kN/m2) were significantly reduced in the MHC type I fibers by 24 and 15%, respectively. In 30-mo-old animals, the peak active force declined by 40% (4.7 +/- 0.2 x10(-4) vs. 2.8 +/- 0. 3 x10(-4) N) and the peak specific tension declined by 30% (79 +/- 5 vs. 55 +/- 4 kN/m2). The maximal unloaded shortening velocity of the MHC type I fibers increased in 12-mo-old animals (from 1.65 +/- 0.12 to 2.59 +/- 0.26 fiber lengths/s) and in 30-mo-old animals (from 0.90 +/- 0. 09 to 1.50 +/- 0.10 fiber lengths/s) after HU. Collectively, these data suggest that the effects of HU on single soleus skeletal muscle fiber function occur in both age groups; however, the single MHC type I fibers from the older animals show greater changes than do single MHC type I fibers from younger animals.     

Individual differences in spatial memory and striatal ChAT activity among young and aged rats

Individual differences in spatial memory among young and aged rats were assessed using memory tasks related to integrity of the hippocampus and the neostriatum. Relationships were then examined between measures of spatial memory and regional choline acetyltransferase (ChAT) activity, a marker for cholinergic integrity. Twenty-four-month-old Long-Evans rats were impaired in comparisons with 6-month-old rats on measures of place learning, working memory, reference memory, and perseveration in water-maze tasks. Aged rats that were impaired on one measure of memory, however, were not necessarily impaired on other measures. ChAT activity in the ventromedial and dorsolateral neostriatum of aged rats was significantly reduced in comparisons with young rats whereas no difference was found in the hippocampus. Aged rats with the most ChAT activity in the anterior ventromedial neostriatum performed best on the place-learning and reference memory tasks but also made the most perseverative errors on the working memory task. In addition, young and aged rats with the most ChAT activity in the anterior dorsolateral neostriatum were those with the least accurate working memory. No relationships were found between ChAT activity in the hippocampus and spatial memory. Thus age-related memory impairment has components that can be segregated by measuring relationships between cholinergic integrity in subregions of the anterior neostriatum and memory tasks with different strategic requirements.     

Maze learning and morphology of frontal cortex in adult and aged basal forebrain-lesioned rats

Maze performance and morphology of frontal cortex were assessed in young adult, middle-aged, and aged rats with and without lesions of the nucleus basalis magnocellularis. Although maze performance did not vary with age, neuron number and the thickness of superficial laminae were reduced in aged rats. Lamina II-III neurons were hypertrophied in middle-aged rats relative to both younger and older groups. At all ages, lesions significantly impaired maze performance. In young adult rats, lesions moderately reduced the size of lamina II-III neurons. This effect was more pronounced in middle-aged rats. Lesions in aged rats did not affect neuron size. The neuronal changes seen in middle-aged rats may reflect a compensatory response to the expression of other age-related neuronal changes, which may affect the ability of cortical neurons to respond to lesion-induced loss of cholinergic input.     

Responses of circulating urea cycle and branched-chain amino acids to feeding in adult and aged Fischer-344 rats

The goal of our study was to identify cytokine combinations that would result in simultaneous ex vivo expansion of both the megakaryocyte (Mk) and granulocyte lineages, since these cell types have the potential to reduce the periods of thrombocytopenia and neutropenia following chemotherapy. We investigated the effects of cytokine combinations on expansion of the Mk (CD41a+ cells and colony forming unit [CFU]-Mk) and granulocyte (CD15+ cells and CFU-granulocyte/monocyte [GM]) lineages. Peripheral blood CD34+ cells were cultured in serum-free medium with interleukin 3 (IL-3), stem cell factor (SCF), and various combinations of thrombopoietin (TPO), IL-6, GM-CSF, and/or G-CSF. The Mk lineage was primarily influenced by TPO in our cultures, although Mk and CFU-Mk numbers were increased when TPO was combined with IL-6. The primary stimulator of the granulocyte lineage was G-CSF, although many synergistic and additive effects were observed with addition of other factors. Expansion of CFU-GM increased upon addition of more cytokines. The cytokine combination of IL-3, SCF, TPO, IL-6, GM-CSF and G-CSF produced the greatest number of granulocytes and CFU-GM. The minimum cytokines necessary for expansion of both the Mk and granulocyte lineages included TPO and G-CSF, since no other factors examined could increase Mk and granulocyte numbers to the same extent. The number of hematopoietic progenitors produced in our culture system should be sufficient for successful engraftment following myelosuppressive therapy if produced on a scale of about one liter.     

Intracerebral haemorrhage in a young adult: consider amphetamine abuse

We present the case of a young female who suffered a massive intracerebral bleed following the ingestion of a small quantity of amphetamine (speed). Physicians should be aware that amphetamine abuse can lead to cerebrovascular events in young adults.     

Estrogen-induced changes in place and response learning in young adult female rats.

Many findings suggest that changes in circulating estrogen levels influence cognition, in some cases impairing performance and in others enhancing performance. One interpretation of these mixed effects is that estrogen biases the strategy used to solve a task. To test this idea, young adult female rats, ovariectomized for 21 days, were trained after acute hormone or control treatment in 2 very similar tasks with different cognitive requirements. One task required place learning and the other response learning. Rats given two 10-μg injections of estradiol 48 and 24 hr before training learned the place task significantly faster than did rats without estradiol. Conversely, rats without estradiol performed better on the response task than did rats with replacement. These data suggest that the cognitive actions of estrogen may be task-specific by modulating the relative contribution of different learning and memory systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)