Plasma corticosterone and renin activity during two-way active avoidance learning in spontaneously hypertensive and Wistar-Kyoto rats

The spontaneously hypertensive rat (SHR) exhibits increased sympathetic and behavioral responses to several types of environmental stress compared to its normotensive progenitor, the Wistar-Kyoto rat (WKY). The aim of the present study was to investigate response-dampening mechanisms in the SHR. This study examines whether learning to control a stressful environment reduces behavioral and neuroendocrine activation in the SHR. Twelve SHR and 12 WKY were subjected to daily sessions (S) of 20 trials of signaled two-way active avoidance. Another 12 SHR served as maturation controls. Blood samples were collected immediately after S 1, S 5, and S 14 and plasma level of corticosterone (p-CS) and plasma renin activity (PRA) were measured. There was an insignificant tendency for the SHR to exhibit larger increases in p-CS in response to stress than the WKY did. By S 5 both groups had attained the avoidance task. However, the level of p-CS was the same as after S 1, showing that activation is independent of the number of shock pulses received and performance. Postsession p-CS decreased between S 5 and 14, slightly more so in the SHR than in the WKY. The SHR exhibited lower PRA than the WKY, but there were no significant effects of exposure to the avoidance schedule. Behaviorally, the SHR exhibited shorter latency to escape in the first trial than the WKY did. The SHRs were hyperactive compared to the WKY, showing more ambulation and rearing behavior. The maturation control SHR reached the same mean arterial pressure as the SHRs which were tested. After S 14, signal duration was shortened from 10 to 3 s for six additional sessions. Both p-CS and PRA increased, while at the same time ambulation and rearing behavior decreased. These data show that the relationship between behavioral control and adrenocortical activation is normal in the SHR in spite of differences in behavior. The present results also confirm previous data on hyperreactivity to footshocks in two-way active avoidance tasks in the SHR.     

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.     

The spontaneously hypertensive rat as an animal model of attention-deficit hyperactivity disorder: effects of methylphenidate on exploratory behavior

Spontaneously hypertensive rats (SHR) show a pervasive hyperactivity in several paradigms. Thus, these rats may be used as an animal model of childhood hyperactivity also called Attention-Deficit Hyperactivity Disorder. This disorder is frequently treated with psychomotor stimulant drugs, but little is known about the effects of such drugs on behavior. The present study investigated the behavioral effects of 1-24 mg/kg methylphenidate (Ritalin) on the exploratory behavior of male SHR and Wistar-Kyoto control rats (WKY) in a two-compartment free-exploration open field. Except following very high doses. SHR spent most of the session time in the field while WKY stayed in the home cage. Low and medium doses were followed by increased activity in the field for SHR and increased activity in the cage for WKY. The response-stimulatory effects of low to medium doses of methylphenidate are less in SHR than in WKY. Starting at medium doses, activity decreased and stereotyped behavior increased progressively by increasing dose. Locomotor activity in the field decreased following lower doses than locomotor activity in the cage, and vertical activity (rearing) was reduced by lower doses than horizontal activity (crossing). The following conclusions were drawn. (i) There is no "paradoxical" inhibition of SHR hyperactivity following methylphenidate. On the contrary, SHR activity is in fact stimulated, albeit to a lesser degree than that of WKY. (ii) The stimulatory effects of low to medium doses are, in general, most pronounced for the kind of exploratory behavior most frequently used by the rat during baseline conditions. (iii) Rearing might be more susceptible to adverse effects of methylphenidate than ambulation.     

Independence of blood pressure and locomotor hyperactivity in normotensive and genetically hypertensive rat

The spontaneously hypertensive rat (SHR) exhibits locomotor hyperactivity in comparison to its normotensive progenitor Wistar-Kyoto (WKY) strain. We asked whether the hyperactive behavior was a direct consequence of elevated blood pressure in the hypertensive rat. Three experimental protocols were used to chronically alter blood pressure. In the first protocol, a group of adult SHRs was given hydralazine (20 mg/kg/day) in their drinking water to lower blood pressure. These animals exhibited a significant decrease in blood pressure, but no change in locomotor activity. In the second protocol, young SHRs (4 weeks of age) were treated with the same dosage of hydralazine until 16 weeks of age. Blood pressure was significantly decreased in these animals with no change in locomotor activity. In the third protocol, normotensive WKY and Sprague-Dawley (SD) rats were made hypertensive with unilateral renal clips. The resulting increase in blood pressure in these animals did not alter locomotor activity. These results suggest that locomotor hyperactivity is an inherent property of the SHR and is independent of blood pressure.     

Neophobia in spontaneous hypertensive (SHR) and normotensive control (WKY) rats

Latency of approaching a novel object (white-colored cube) placed in an unfamiliar open field, duration of object exploration, ambulation, rearing, grooming, and defecation were investigated in spontaneous hypertensive rats (SHR), their genetic normotensive controls (WKY), and standard Laboratory rats of Wistar origin (Tif:RAIf). The parameters measured were taken as indices of fear due to novelty (neophobia). Remarkable differences in behavior of all three strains were observed. By comparison to RAIf and WKY rats, SHR showed decreased neophobia as reflected in the significantly shorter latency of approaching the object and enhanced ambulation and rearing activity in the open field. By comparison to RAIf rats SHR also showed reduced grooming and defecation. WKY rats distinguished themselves from both SHR and RAIf by almost total absence of all responses in this test situation. This behavioral suppression was antagonized by 7.5 mg/kg ip of chlordiazepoxide. The results of this study further support the notion that, by comparison to standard laboratory rats, both SHR and WKY rats show possible genetically determined, altered behaviors which are diametrically opposite to each other.     

Exploration, fear and maze learning in spontaneously hypertensive and normotensive rats

In this study the performance of normotensive (WKY) rats was compared with that of hypertensive (SHR) rats on a Novel Object Test, a standardized Fear Test, and the Hebb-William's maze. We found no strain differences for exploration; however, WKY rear and ambulate more than SHR near the walls of the apparatus. There were no strain differences apparent in the Fear Test. WKY showed markedly different behavior compared with SHR on the Hebb-William's maze; WKY showed a high level of stereotyped displacement behaviors and failed to improve their performance over successive trials. Overall, WKY appear to be more reactive to environmental conditions than SHR. The behavior of both strains is highly context dependent.     

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.     

Open-field behavior in two models of genetic hypertension and the behavioral effects of salt excess

In order to assess the relationship of behavior to blood pressure and salt intake, open-field behavior was studied in 123 rats of the spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), Sprague-Dawley (SD), and Dahl resistant (DR) and sensitive (DS) strains. DS rats become hypertensive upon exposure to either high dietary salt or psychogenic stress, while DR rats remain normotensive. A circular photobeam open field was used under full room illumination. Three 5-min trials were given on consecutive days. Rats were tested with or without 5 days of an 8% NaCl diet. We found that DS rats were less active than DR rats, regardless of diet. In contrast, SHR rats were more active than WKY rats. However, DS and SHR rats were equally active. Thus, behavioral differences between these two models of hypertension are expressed by the normotensive control strains. The relative ranking of activity levels between strains was DR = SD greater than SHR = DS greater than WKY. High-salt-enhanced intertrial habituation, defined as the decrease in activity across trials (DS, 100%; SD, 82%; SHR, 90%; WKY, 1350%; but DR, -50%) as well as intratrial habituation, defined as the decrease from the first to the second half of the trial (14%, all subjects). Defecation was increased with high salt (DS, 975%; SD, 59%; SHR, 267%; WKY, 89%; but DR, 40%). These effects of high salt may reflect an increase in an emotionality factor. DR rats were largely resistant to the behavioral effects of salt. Total activity was positively correlated with blood pressure in hypertensive rats, r(42) = 0.33, p less than .01, but negatively correlated in normotensive rats, r(81) = -0.34, p less than .01. The proportion of total activity occurring in the first half of the trial for the initial test day was correlated with blood pressure in normotensive rats r(81) = 0.44, p less than .01. Dietary salt excess has behavioral as well as cardiovascular consequences.     

Behavioral hyperreactivity in the spontaneously hypertensive rat compared to its normotensive progenitor

The spontaneously hypertensive rat (SHR) is an excellent model of essential hypertensive disease. Hyperreactivity has been postulated as a contributing factor in the development of high blood pressure in the SHR and in man. In the maturing organism recurring hypertensive stress responses may promote permanent vascular changes and result in a fixed hypertension. Simple behavioral activity and emotionality rating scales were used to compare a large number of SHR with equally large groups of closely-related and distantly-related normotensive rats. As predicted, the SHR were clearly more active and emotional than their ancestral Wistar Kyoto (WKY) strain. However, the distantly-related normotensive Wistars did not differ from the SHR in either activity or emotionality. These results indicate that behavior and hypertension are not necessarily related in the rat. Nonetheless, the behavioral differences between the SHR and their closest genetic match, the WKY, suggest that arousal and blood pressure levels may be causally linked in this case of naturally occurring hypertension.     

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.     

Lifelong hyperarousal in the spontaneously hypertensive rat indicated by operant behavior

Instrumental conditioning techniques were used to obtain objective evidence of differences in behavioral arousal between the spontaneously hypertensive rat (SHR) and the normotensive ancestral Wistar Kyoto (WKY) strain. Subjective emotionality ratings previously indicated that the genetically hypertensive rats were more active and aggressive than their normotensive cousins. In a lengthy series of operant conditioning sessions using a small number of adult female SHR and WKY rats, hyperarousal in the SHR was confirmed by their significantly higher response outputs on either response contingent or time contingent schedules of reinforcement. Conditioned emotionality tests during this series of experiments also suggested hyperarousal and aggressiveness in the SHR, since the fear-conditioned stimulus suppressed bar-pressing in the SHR much less than in the WKY. Further experiments with young prehypertensive SHR rats provided the same evidence of hyperresponsivity in the SHR compared to the WKY strain. Furthermore, these young SHR failed to develop hypertension by the end of the study (14 weeks of age), while their nonconditioned SHR cousins had become clearly hypertensive by the same age. This suggests that factors related to the conditioning methods modified the development of high blood pressure in this animal model of essential hypertension.     

Inbreeding of Wistar-Kyoto rat strain with hyperactivity but without hypertension

A genetic inbreeding program using Wistar-Kyoto rat strains as progenitors was used to combine the hyperactivity trait of the spontaneously hypertensive rat (SHR) with the normotensive trait of the WKY genetic control strain. From an SHR X WKY cross we produced a gene-assorting F2 population from which selected brother-sister matings were carried out through seven successive inbred populations. This program produced a new strain of hyperactive rats with normotensive mean systolic blood pressure levels, and we have designated the new strain as the Wistar-Kyoto hyperactive (WK/HA) rat. Another behavioral characteristic of the SHR rat, poor habituation in a nonreinforcing novel environment, did not appear as a characteristic trait of the new strain of WK/HA rats, suggesting a separate underlying genetic basis for the two traits that had been apparently fortuitously fixed in the SHR genotype as a result of intensive inbreeding of that strain. The new WK/HA strain, together with the WKY control strain, is considered as more suitable for subjects in studying hyperactivity in rats than the original SHR strain with its concomitant hypertension and poor habituation traits.     

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.     

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.     

Open-field behavior of spontaneously hypertensive and Wistar-Kyoto normotensive rats: effects of reciprocal cross-fostering

The influence of the maternal environment on the development of open-field behavior in spontaneously hypertensive (SHR) rats was investigated using the technique of reciprocal cross-fostering. Entire litters of SHR and Wistar-Kyoto (WKY) normotensive rats were either reared by their natural mothers, in-fostered to dams of the same strain, or cross-fostered to dams of the opposite strain on the day after birth. Open-field behavior was assessed in male and female rats from the six groups (2 strains x 3 rearing conditions) at 30, 60, 90, and 120 days of age. Animals were observed in the open-field during a 5-min test period and the number of squares entered and hindlimb rears were recorded. At all ages tested, SHR rats were more active in the open field, entering more squares and rearing more frequently than WKYs. SHR females were more active than age-matched SHR males, while no sex differences were apparent in the WKY strain. At each age, open-field behavior was similar across WKY rearing groups. SHR control and in-fostered animals responded similarly in the open field; however, SHR cross-fostered rats (particularly females) tended to be more active than controls. Although cross-fostering has profound effects on cardiovascular development and functioning in the SHR, it appears that altering the early maternal environment experienced by SHR pups does not grossly affect the development of open-field behavior.     

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.     

Gender differences in acute and chronic stress in Wistar Kyoto (WKY) rats

While females are considered more susceptible to depressive behavior, this assertion is not strongly supported by the experimental literature. Since stress contributes to depressive behavior, male and female Wistar Kyoto (WKY) rats were exposed to either one session (acute stress) or 5 sessions (chronic stress) of restraint plus cold in order to study depressive behavior in male and female rats. After their respective treatment exposure, rats were tested in the open field test (OFT) and for retention of a passive-avoidance (P-A) task. One stress session resulted in significant immobility in the OFT for males, whereas 5 sessions were required to produce similar immobility in female rats. Acute stress interfered with the retention of the P-A response for males, while both acute and chronic stress produced poor P-A responses in female rats. Food consumption decresed, progressively, as a function of stress sessions, in female rats, whereas feeding in males returned to control levels after five stress days. Both acute and chronic stress exacerbated the stress ulcer response in male rats, but not in female rats. Chronic, but not acute, stress resulted in an increase in serotonin transporter mRNA levels in the dorsal raphe nucleus of both male and, female rats. The general consensus from these data suggested that female rats were more vulnerable to chronic stress and consequently supported the notion that females may be more susceptible to stress induced behavioral depression.     

一个中枢炎性免疫诱发长时程抑郁样行为的新模型

脂多糖(lipopolysaccharide, LPS)免疫激活模型是研究抑郁症细胞因子假说的重要动物模型, 目前国际上常用外周单次LPS注射诱发抑郁样行为, 但该模型中抑郁样行为持续仅有数小时。为建立诱发较长时程抑郁样行为的免疫激活动物模型, 本研究尝试侧脑室注射LPS激活大鼠中枢免疫炎性反应, 考察单次以及重复中枢LPS注射诱发抑郁样行为的效果, 以及中枢炎性免疫诱发行为改变的时程。结果显示：单次中枢LPS注射后24 h只能诱发旷场自发活动和探索行为下降等部分抑郁样行为, 未能诱导糖水偏好下降和悬尾不动时间增加; 3次重复注射则在末次LPS注射后24 h表现出显著的糖水偏好下降, 自发活动和探索行为减少, 悬尾不动时间增加等行为。且自发活动、探索行为减少和悬尾不动时间增加能够延续至末次LPS注射后72 h。这些结果表明脑室重复LPS注射可诱发较长时程的抑郁样行为, 这种新的中枢炎性免疫激活诱发的抑郁症模型, 为研究抑郁症炎性免疫机制提供了更为有效的动物模型, 有助于深入探讨行为和免疫功能间的复杂关系。     

Gender differences in acute and chronic stress in Wistar Kyoto (WKY) rats.

While females are considered more susceptible to depressive behavior, this assertion is not strongly supported by the experimental literature. Since stress contributes to depressive behavior, male and female Wistar Kyoto (WKY) rats were exposed to either one session (acute stress) or 5 sessions (chronic stress) of restraint plus cold in order to study depressive behavior in male and female rats. After their respective treatment exposure, rats were tested in the open field test (OFT) and for retention of a passive-avoidance (P-A) task. One stress session resulted in significant immobility in the OFT for males, whereas 5 sessions were required to produce similar immobility in female rats. Acute stress interfered with the retention of the P-A response for males, while both acute and chronic stress produced poor P-A responses in female rats. Food consumption decreased progressively, as a function of stress sessions, in female rats, whereas feeding in males returned to control levels after five stress days. Both acute and chronic stress exacerbated the stress ulcer response in male rats, but not in female rats. Chronic, but not acute, stress resulted in an increase in serotonin transporter mRNA levels in the dorsal raphe nucleus of both male and female rats. The general consensus from these data suggested that female rats were more vulnerable to chronic stress and consequently supported the notion that females may be more susceptible to stress-induced behavioral depression. Key Words: WKY rats, acute and chronic stress, gender, passive avoidance, open field behavior, stress-ulcer, adrenal weight, serotonin, dorsal raphe nucleus     

Time-dependent changes in inaccessible memory

The present experiment examined whether forgetting of contextual attributes—the loss of discriminability of background stimulus features over time—also occurs when a memory remains inaccessible (amnestic) during the retention interval. To examine this issue, rats received an acute hypothermia treatment that caused reversible anterograde amnesia for a passive-avoidance task and were tested 1 or 7 days later in either the same or a different context. At the short retention interval, the subjects discriminated between the contexts, as evidenced by the finding that reversal of amnesia occurred only in the training context. However, at the 7-day interval, recovery of the avoidance response was induced in either context, reflecting the forgetting of differentiating characteristics. These findings indicate that inaccessible memory remains susceptible to processes of modification and distortion that typically influence intact memories.