Behavioral studies in spontaneously hypertensive rats

In the present study we examined some behavioral patterns in spontaneously hypertensive (SHR) male rats as compared with Wistar (W) rats. The following methods were employed: open field test, two-way active avoidance, passive avoidance, shock-induced fighting, shock-induced suppression of drinking (conflict test), and dominant-subordinate behavior in rats competing for water. Spontaneously hypertensive rats showed higher level of locomotor activity, lower emotionality, lower anxiety level, increased acquisition of avoidance tasks, and enhanced dominance behavior. In addition, hypertensive rats were less aggressive in shock-induced fighting test. It is concluded, that spontaneously hypertensive rats seem to be hyperactive in terms of locomotor activity while their emotionality appears to be paradoxically reduced.     

Residential-maze behavior of spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) exhibit elevated levels of ambulation after transfer to a novel environment compared to the Wistar-Kyoto rat (NR). The present experiment compared long-term activity of SHR and NR in a residential maze to determine whether the SHR exhibit elevated levels of locomotor activity under undisturbed, baseline conditions in addition to enhanced reactivity to stimuli. The SHR were much more active visiting more arms of the maze than the NR during the initial hours following transfer to the maze, and during hours around dark onset and light onset. However, the SHR also exhibited higher levels of activity than the NR under baseline conditions. While the NR visited the arm containing food more frequently than other arms, the SHR exhibited no such preference. These data show that both stimulus-induced and basal levels of ambulation are increased in the SHR compared to its normotensive genetical counterpart.     

Passive-avoidance behavior of spontaneously hypertensive rats

Spontaneously hypertensive rate (SHR) generally exhibit higher performance in avoidance tasks than Wistar-Kyoto control rats (WKY) do. The SHR are more active than the WKY after transfer to a novel environment and after electric footshocks. The present study examined the performance, behavior, and plasma corticosterone of young male SHR and WKY in a passive-avoidance task in which high levels of locomotor activity do not facilitate performance. The effects of three levels of discriminability of the safe area were studied. Passive-avoidance performance was statistically significantly lower in the SHR, but the difference was small. There was no difference between the SHR and the WKY in post-test plasma-corticosterone levels, and there was no relationship between ambulation and plasma-corticosterone levels. The behavioral differences between the SHR and the WKY varied as a function of the discriminability of the safe area. Specifically, in the low-discriminability condition, ambulation, but not rearings, was equally suppressed in the SHR as in the WKY and there was no difference in immobility. In the high-discriminability condition the SHR exhibited more ambulation, more rearing, and less immobility than the WKY. These data confirm that the SHR exhibit an increased tendency for facilitation of locomotor activity during activation compared to the WKY. Because the passive-avoidance performance of the SHR was lower than that of the WKY, these data suggest that previous reports of superior avoidance learning in the SHR reflect their elevated level of locomotor activity rather than an improved ability to acquire conditioned responses. Ability to discriminate stimuli seems to be normal in the SHR since ambulation was modified according to stimulus parameters.     

Water deprivation associated with operant conditioning inhibits hypertensive disease in young spontaneously hypertensive rats

The development of high blood pressure in young spontaneously hypertensive rats (SHR) is inhibited by operant conditioning motivated by chronic water deprivation. The present study showed that the inhibition of hypertension was not due to the operant conditioning,per se, but was a result of chronic water deprivation (23.5 hr schedule) imposed on the rats from five through 12 weeks of age. Blood pressures were measured directly using a carotid artery cannula and light enflurane anesthesia. The behaviorally conditioned SHR and the water-deprived SHR controls had equal blood pressures and were significantly less hypertensive than untreated or enriched environment SHR groups. The antihypertensive action of water deprivation was not detected by weekly indirect blood pressure measurements made in the awake state. Nonetheless, the chronicity of the deprivation-induced inhibition of hypertension was confirmed by a lesser degree of left ventricular hypertrophy in the deprived SHR relative to the nondeprived SHR. Our behavioral results again demonstrated hyperreactivity in the SHR relative to the Wistar Kyoto (WKY). This behavioral hyperreactivity in the SHR may explain the exaggerated increase in drinking in the deprived SHR groups when returned toad lib conditions. The data of this study and our previous work suggest that arousal differences between SHR and WKY strains are more reliably differentiated by fixed interval schedules of reinforcement than by a fixed ratio schedule. Hyperarousal may precede hypertension in the SHR, but it is undetermined whether hypertension can be found in the absence of hyperarousal in these rats.     

Accelerated development of cardiac sympathetic responses in spontaneously hypertensive (SHR) rats

The functional development of cardiac and adrenal medullary responses to reflex activation of the sympathetic nervous system was studied in preweanling spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats. Pups of the two strains received injections of insulin or saline at 2, 4, 8, 12, or 16 days of age and were sacrificed 3 h later. Insulin administration produces a significant decrease in circulating levels of glucose which in turn results in a centrally mediated increase in sympathetic outflow. The induction of ornithine decarboxylase (ODC) in heart and the depletion of epinephrine from the adrenal medulla served as tissue markers of functional sympathetic neurotransmission. WKY and SHR pups had comparable levels of ODC activity in heart under basal conditions. In contrast, levels of catecholamines in the adrenals were greater in SHR pups at 2 and 4 days of age. Following insulin administration, SHR pups exhibited a greater induction of cardiac ODC activity at 2, 4, and 8 days of age compared to age-matched WKY controls. However, there were no differences between SHR and WKY pups in the magnitude of the adrenal medullary response to insulin-induced hypoglycemia. These alterations in sympathetic-target tissue development during the first postnatal week of life may contribute in part to the higher arterial pressures maintained by SHRs throughout the lifespan.     

Categorization and cognitive deficits in compulsive hoarding

According to the cognitive-behavioural model of compulsive hoarding, information-processing deficits in the areas of attention, memory, decision-making, and categorization contribute to hoarding behaviour. The purpose of the current study was to examine whether individuals with compulsive hoarding exhibited impairment on executive functioning and categorization tasks. Three groups of participants were recruited (N = 60): individuals with compulsive hoarding syndrome, individuals with an Axis I mood or anxiety disorder, and non-clinical control participants. All participants completed self-report measures of cognitive difficulties, neuropsychological tests of executive functioning and decision-making, and four categorization tasks. Results suggested that hoarding participants reported more cognitive failures and more problems with attention and decision-making than non-clinical control participants. In addition, hoarding participants performed worse than both control groups on the Stockings of Cambridge (SOC), a neuropsychological test of planning ability, and were slower and more anxious during a categorization task. These findings suggest that specific deficits in executive functioning may be associated with the difficulties hoarding patients have organizing their possessions.     

Stress ulcer and open-field behavior of spontaneously hypertensive,normotensive, and Wistar rats

Spontaneously hypertensive rats (SHRs) and the normotensive Wistar/Kyoto (WKY) rat were observed, along with Wistar rats (which represent the parent strain), on various open-field behaviors. All three strains were subsequently exposed to the activity-stress (A-S) ulcerogenic procedure. SHR and Wistar rats were very active in most open-field measures as compared with WKY rats, but only SHRs were active during the A-S treatment. WKY rats were very ulcer prone and had significantly more ulcers than SHRs, which in turn had more ulcers than Wistar rats. It was anticipated that Wistar rats would resemble the WKY rats, but in most measures the Wistars resembled the SHRs. The study suggests that although WKY rats function as an appropriate control for hypertension studies, these rats may be inappropriate as controls for other physiological and behavioral studies.     

Adult blood pressure reduction in spontaneously hypertensive rats reared by normotensive Sprague-Dawley mothers.

Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) normotensive, and Sprague-Dawley (SD) normotensive rats were either reared by their natural mothers (controls) or fostered to a mother of one of the other strains. The effects of rearing environment were assessed by measures of body weight at weaning and adult resting mean arterial blood pressure (MAP) and heart rate (HR). At weaning, SHR control rats weighed less than WKY controls which in turn weighed less than SD controls. SHR and WKY rats reared by SD mothers weighed significantly more than their respective controls, whereas SD rats reared by either SHR or WKY mothers weighed less than SD control rats. Manipulation of the maternal environment was attended by a change in adult resting MAP in only one group. SHR rats reared by SD mothers had MAPs which were significantly lower than SHRs reared by their natural mothers. No within-strain adult HR differences were observed between control and cross-fostered groups. These data indicate that the effects of cross-fostering on adult resting MAP previously reported for SHR and WKY animals are generalizable to another normotensive strain. That is, genetically hypertensive (SHR) animals exposed to a normotensive (WKY or SD) maternal environment display a reduction in adult resting MAP, whereas hypertension or an increase in adult MAP is not induced in normotensive rats (WKY or SD) as a consequence of exposure to a hypertensive maternal environment.     

Contrasting lever-press avoidance behaviors of spontaneously hypertensive and normotensive rats (Rattus norvegicus)

Lever-press avoidance performances of Spontaneously Hypertensive (SHR) and Wistar-Kyoto (WKY) rats were observed in two experiments. The first compared them at shock intensities of 1 or 2 mA. The SHRs had the highest percentage of avoidances, made the most coping responses (avoidances plus escapes), and received the fewest shocks (ps less than .05). They also had shorter avoidance and initial-escape latencies (ps less than .05). In the second experiment these strains were trained with signal-shock intervals that produce good (60 s) or poor (10 s) avoidance acquisition. Analysis of the Strain x Conditions x Blocks interaction showed that SHRs performed better with the longer interval (p less than .05), whereas WKYs' performance was similar with both (p greater than .05). Thus WKYs differed from all other strains previously exposed to these conditions. The findings are interpreted in terms that emphasize the SHRs' tendency to move, compared with the WKYs' tendency to freeze in response to aversive stimuli, rather than characterizing SHRs as hyperreactive.     

Recognition memory deficits in mild cognitive impairment

ABSTRACT There is no agreement on the pattern of recognition memory deficits characteristic of patients diagnosed with mild cognitive impairment (MCI). Whereas lower performance in recollection is the hallmark of MCI, there is a strong controversy about possible deficits in familiarity estimates when using recognition memory tasks. The aim of this research is to shed light on the pattern of responding in recollection and familiarity in MCI. Five groups of participants were tested. The main participant samples were those formed by two MCI groups differing in age and an Alzheimer's disease group (AD), which were compared with two control groups. Whereas one of the control groups served to assess the performance of the MCI and AD people, the other one, composed of young healthy participants, served the purpose of evaluating the adequacy of the experimental tasks used in the evaluation of the different components of recognition memory. We used an associative recognition task as a direct index of recollection and a choice task on a pair of stimuli, one of which was perceptually similar to those studied in the associative recognition phase, as an index of familiarity. Our results indicate that recollection decreases with age and neurological status, and familiarity remains stable in the elderly control sample but it is deficient in MCI. This research shows that a unique encoding situation generated deficits in recollective and familiarity mechanisms in mild cognitive impaired individuals, providing evidence for the existence of deficits in both retrieval processes in recognition memory in a MCI stage.     

Component analyses differentiate between exploratory behaviour of spontaneously hypertensive rats and Wistar Kyoto rats in a two-compartment free-exploration open field

The present study investigated behaviour in a two-compartment free-exploration open field by means of a component analysis. Seven spontaneously hypertensive rats (SHR) and six normotensive Wistar Kyoto control rats (WKY) were tested repeatedly on eight behaviour parameters in this apparatus. A two-compartment free-exploration open field evokes less fear than the standard one-compartment forced-exploration open field, because it permits the rat to enter the field from its home cage. The data were subjected to principal component analysis and multivariate analysis of variance. The results showed that the recorded behaviour grouped into two independent components, encompassing behaviour in the cage and in the field, respectively. These components are interpreted as reflecting different kinds of exploration: (i) distant exploration when the rat explores from its home cage, and (ii) close exploration when the rat explores by entering the novel field. The SHR scored highest on both, although they mostly used close exploration. In the WKY rats, which mainly stayed in their cages, distant exploration was predominant. The present free-exploration open-field procedure discriminates between two different exploration strategies employed by SHR and WKY rats.     

Maternal behavior of spontaneously hypertensive and Wistar-Kyoto normotensive rats: effects of reciprocal cross-fostering of litters

Maternal behavior of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive dams rearing either their natural pups or pups of the opposite strain was assessed when pups were 4-6 days of age. Consistent with previous reports, SHR dams caring for their natural pups were observed nursing and licking their pups more often than WKY dams and were away from their pups less often. The behavior of dams rearing cross-fostered pups demonstrated that this strain difference in patterns of maternal behavior is dependent on pup type. Mothers of both strains shifted their behavior in the direction of the opposite strain's maternal behavior pattern when caring for cross-fostered pups. This shift was most pronounced in SHR dams caring for WKY pups. These data suggest that alterations in patterns of maternal behavior produced by cross-fostering may play an important role in cross-fostering effects on the physiological development of SHRs previously reported.     

Voluntary exercise ameliorates cognitive deficits in morphine dependent rats: the role of hippocampal brain-derived neurotrophic factor

Chronic exposure to opiates impairs spatial learning and memory. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we investigated whether voluntary exercise would ameliorate the cognitive deficits that are induced by morphine dependence. If an effect of exercise was observed, we aimed to investigate the possible role of hippocampal brain-derived neurotrophic factor (BDNF) in the exercise-induced enhancement of learning and memory in morphine-dependent rats. The rats were injected with bi-daily doses (10mg/kg, at 12h intervals) of morphine over a period of 10 days of voluntary exercise. Following these injections, a water maze task was performed twice a day for five consecutive days, followed by a probe trial 2 days later. A specific BDNF inhibitor (TrkB-IgG chimera) was used to block the hippocampal BDNF action during the 10 days of voluntary exercise. We found that voluntary exercise blocked the ability of chronic morphine to impair spatial memory retention. A blockade of the BDNF action blunted the exercise-induced improvement of spatial memory in the dependent rats. Moreover, the voluntary exercise diminished the severity of the rats' dependency on morphine. This study demonstrates that voluntary exercise ameliorates, via a TrkB-mediated mechanism, the cognitive deficits that are induced by chronic morphine. Thus, voluntary exercise might be a potential method to ameliorate some of the deleterious behavioral consequences of the abuse of morphine and other opiates.     

The relation between cognitive deficits and schizophrenic symptoms]

Reasons are given for explicitly derived requirement that experimental-psychological investigations of cognitive deficits of schizophrenics should be related to their clinical symptoms. Results which verify this relations prove to be relevant for prognosis, therapy and rehabilitation of schizophrenic patients.     

Common and specific cognitive deficits in schizophrenia: relationships to function

The goals of the present study were to assess the interrelationships among tasks from the MATRICS and CNTRACS batteries, to determine the degree to which tasks from each battery capture unique variance in cognitive dysfunction in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects were 104 schizophrenia patients and 132 healthy control subjects recruited as part of the CNTRACS initiative. All subjects completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal Learning Test. Functional outcome was also assessed in the schizophrenia subjects. In both the patient and control groups, we found significant intercorrelations between all higher order cognitive tasks (episodic memory, goal maintenance, processing speed, verbal learning) but minimal relationships with the visual task. For almost all tasks, scores were significantly related to measures of functional outcome, with higher associations between CNTRACS tasks and performance-based measures of function and between one of the MATRICS tasks and self-reported functioning, relative to the other functioning measures. After regressing out variance shared by other tasks, we continued to observe group differences in performance among task residuals, particularly for measures of episodic memory from both batteries, although these residuals did not correlate as robustly with functional outcome as raw test scores. These findings suggest that there exists both shared and specific variance across cognitive tasks related to cognitive and functional impairments in schizophrenia and that measures derived from cognitive neuroscience can predict functional capacity and status in schizophrenia.     

Commentary on two articles concerning generalized and specific cognitive deficits

This is a commentary on essays in this journal issue by M. E. Strauss (2001) and R. A. Knight and S. M. Silverstein (2001) on research methodology for studying cognitive deficits. Concentrating mostly on Knight and Silverstein's article, the authors review the psychometric issues in the matched-task design, analyze Knight and Silverstein's "process-oriented" objections to that design, and scrutinize their methods for studying cognitive deficits, examining 2 of their empirical studies as examples of those methods.     

Depressive deficits in memory: focusing attention improves subsequent recall.

Ss diagnosed as depressed, recovered from depression, or without a history of depression performed an unintentional learning task, followed by tests of free and forced recall. In the learning task, Ss decided whether a series of nouns sensibly completed corresponding sentence frames that varied in decision difficulty. For half of the Ss, the focus of attention was unconstrained by the demands of this task. The others, however, were required to repeat the targeted noun at the end of the trial as a means of focusing their attention on the task. Depressed Ss in the unfocused condition subsequently recalled fewer words than did both control groups, but this deficit disappeared in the focused condition. These results suggest that depression might not fundamentally impair the resources required for good performance on such tasks. The results' relevance to resource-allocation, initiative, and inhibition accounts of depressive deficits in memory is discussed.     

Immunization and reversibility of cognitive deficits due to learned helplessness

Predictions made from the learned-helplessness model received support in three experiments. The effects of response-outcome independence, as well as immunization and reversibility of such effects were demonstrated with human subjects. It was also demonstrated that differences in locus of control, sex and attribution, influenced those results. Furthermore, the effects of modeling and the use of cognitive tasks for both pretreatment and reversibility were examined.