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R Murison

Publications and source records attributed to R Murison.

At least 37 records · Page 2Linked to original sources

Individual behavioral characteristics and extent of stress-induced gastric ulceration in rats.

Individual rats differ amongst themselves with respect to both behavior and the extent of stress-induced gastric ulceration, even though they have been treated identically, are from the same stock, age, etc. The relationship between behavior and ulcer susceptibility is of interest in its own right, and is reminiscent of the extensive body of literature on personality characteristics and disease risk in humans. In the Sprague-Dawley rat, we have found that animals react differentially to the introduction of new stimuli in a previously learned Lashley-maze, and that the increase in latency is negatively related to attack frequency in a classic intruder test. Furthermore, we have found a negative correlation between attack latency in the intruder test and the amount of gastric ulceration induced by restraint-in-water stress. We have further found highly significant relationships between the responses of otherwise untreated animals to a simple startle test and the extent of gastric ulceration induced by restraint-in water stress. We believe that greater notice should be taken of the individual animal's behavioral profile for three reasons. First, prior behavioral screening may be a useful method for reducing error variance. Second, physiological and neuroendocrinological differences between high susceptible and low susceptible individuals are of interest in understanding the psychobiology of stress ulcerations both in animals and humans. Finally, an understanding of the etiology of these individual differences may cast light on links between behavior patterns and stress pathology.

Animals↗

Stress ulceration in rats: impact of prior stress experience.

The role of prior stress experience on the response of the organism to a later stressor has been studied in terms of the extent of gastric ulceration induced by the second stressor. These studies have focused largely on effects of prior stress (shock, restraint, activity) on the ulceration developing under later restraint and activity stress. The studies indicate that prior exposure to restraint stress provides some protection against later restraint ulcer development. Using shock as the prior stressor, the effects on later restraint stress are determined by the particular characteristics of the shock (controllability and predictability), and by contextual factors. Studies are lacking on the significance of these characteristics of shock for later activity stress ulcers. Further studies are required therefore on the significance of psychological characteristics of the prestress, and on the effects of these prestressors at different stages of the life cycle. The identification of these factors, and a clearer picture of the protective and exacerbating effect of prior stress will allow us to explore the physiological (central and peripheral) mechanisms underlying ulcer development and ulcer susceptibility.

Animals↗

Juvenile and adult footshock stress modulate later adult gastric pathophysiological reactions to restraint stresses in rats.

Rats were stressed with (a) signaled footshocks, (b) unsignaled footshocks, or (c) handled without footshocks as a prepubertal juvenile (28-36 days old), as an adult (96 days old), or both. This yielded nine treatment groups (3 x 3). Two days after the adult treatment, all animals were challenged by restraint and partial immersion in water (19 degrees C) to assess their relative susceptibility to gastric erosions ("ulcers"). We found that any prior exposure to footshock stress increased the amount of ulcers; juvenile and adult experiences each produced equal increases but the combination of the two was less ulcerogenic than either alone. The predictability of the footshocks did not modulate ulcerogenicity. Adult corticosterone responses to (a) adult stress and (b) ulcer induction were not related to the observed ulcer severity; however, juvenile footshock stress appeared to reduce the corticoid response to the ulcerogenic challenge but not to the adult footshock stress.

Age Factors↗

Studies on the interaction between ICV effects of CRF and CNS noradrenaline depletion.

The role of an intact locus coeruleus (LC) noradrenergic system for the central effects of corticotropin-releasing factor (CRF) was studied. Rats were treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a highly selective noradrenergic neurotoxin permanently affecting mainly the LC system. This procedure did not affect the activation of the sympathetic nervous system, as measured by plasma catecholamine levels, after either intracerebroventricular (ICV) or intraperitoneal (IP) administration of 8-micrograms CRF. Neither was the increased emotionality seen in an open field test after ICV injection of CRF altered. However, the ulceroprotective effect of 8-micrograms CRF ICV during a 2-hr water restraint stress was significantly antagonized by pretreatment with DSP-4, while CRF did exhibit an ulceroprotective effect after IP administration to DSP-4-treated animals. Our data indicate that the ulceroprotective effect of CRF under restraint stress is, at least partly, dependent on an intact locus coeruleus noradrenergic system.

Animals↗

Plasma corticosterone and restraint induced gastric pathology: age-related differences after administration of corticotropin releasing factor.

Corticotropin releasing factor (CRF) or saline was administered i.p. to rats aged either 100 or 220 days, followed by either brief handling or water immersion restraint. Plasma corticosterone was measured 75 min. later. Age of the animals in itself was not a significant factor either for basal levels of plasma corticosterone or for extent of restraint induced gastric pathology. However after CRF administration, young but not older animals revealed a significant increase in plasma corticosterone levels, and post restraint gastric ulcerations were more severe in older than young animals. CRF significantly decreased the number of restraint induced ulcers in young rats, while the cumulative ulcer length was increased in older animals.

Aging↗

Stress-rest cyclicity in the pathogenesis of restraint-induced stress gastric ulcers in rats.

Temporal patterns of stress and rest have been shown to influence extent of shock-induced pathology. In the present study, the influence of stress-rest cycles was studied on amount of gastric ulceration after two forms of immobilization stress in rats. In Experiment 1, rats were subjected to different patterns of cold supine restraint interspersed with rest periods. A single 180 minute exposure produced more extensive ulceration than did a series of six 30 minute stress periods interspersed with 30 minute rest periods in the home cage. Different results were found in Experiment 2 using the stress of restraint in water and stress/rest patterns parallel to those used in Experiment 1. Previous reports have suggested that a "priming" stress might activate mechanisms protective against gastric ulceration. This was also investigated in Experiment 2 when animals were subjected to either a single 150 minute stress period, a 30 minute priming exposure to the same stressor 150 minutes prior to a 150 minute second exposure, or a 30 minute priming exposure 30 minutes prior to a 150 minute second exposure. No evidence was found for protective effects. In fact, a priming stress 30 minutes prior to final exposure enhanced ulceration. The studies provide some supporting evidence for the role of cycles in determining extent of stress pathology. Such data must be accounted for in any description of the mechanisms of stress-related ulceration.

Animals↗

Hypothalamo-pituitary-adrenal manipulations and stress ulcerations in rats.

Both gastric ulceration and activation of the hypothalamo-pituitary adrenal axis are considered integral to the stress response, and a causal relationship between the two has been suggested. In the present study, corticosterone secretion in rats was either stimulated with CRF or lowered with metyrapone during a known ulcerogenic stress. Reduction of circulating corticosterone during the stress had no effect on ulceration severity compared to saline-treated stressed control rats. Treatment with CRF in stressed animals reduced ulceration severity. The mechanism of this protective effect remains unclear. The findings do not support a simple causal relationship between adrenocortical activity and gastric ulceration.

Animals↗

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.

Animals↗

Poststress effects of danger and safety signals on gastric ulceration in rats.

Gastric ulceration of rats stressed by restraint in 19 degrees C water for 75 min was markedly increased by allowing a 75-min postrestraint room-temperature rest period during which the rat was exposed to cues that had previously been associated with the delivery of 80 5-s uncontrollable electric shocks distributed over four sessions. This effect obtained equally without regard to whether the "danger cues" were punctate signals or constant contextual cues or whether contextual ones were interrupted by punctate safety signals. The experimental treatments used were unusual in that they equated the groups on their total conditioning history and thus allowed a more pure look at the poststress effect than heretofore. Other groups provided controls for prior shocks, rest, and their interaction as well as handling. Analyses of corticosterone after the stress or stress-rest cycle revealed only a general decline in corticosterone levels with rest undifferentiated across groups.

Animals↗

Metabolism of sulfur-containing amino acids by pregnant merino ewes.

The availability and utilization of cystine and methionine were measured in single-bearing Merino ewes on three occasions, approximately 90, 110 and 130 days after mating, and the effects on these traits of sulfur amino acids (SAA) infused into the abomasum were also measured. Two levels of SAA were infused containing 0.5 or 1.0 g day-1 organic sulfur with DL-methionine contributing two-thirds and L-cystine one-third of the supplementary sulfur. The quantity of the diet offered was increased at each occasion so as to maintain maternal liveweight. The rates of irreversible loss of both cystine and methionine from plasma increased as pregnancy advanced, but the ratios between the rates of irreversible loss and intake of digestible organic matter (DOMI) did not vary with stage of pregnancy. The average daily rates of irreversible loss of cystine and methionine by the ewes consuming the diet alone were 13.6 and 119 mmol kg-1 DOMI respectively. The average rates of irreversible loss of methionine (Im, mmol h-1) and of cystine (Ic, mmol h-1) were both linearly (P less than 0.05) related to the rate of infusion of organic sulfur into the abomasum (s, g day-1): Im = 2.44 (+/- 0.33) s + 1.28 (+/- 0.13); and Ic = 0.16 (+/- 0.02) s + 0.30 (+/- 0.01). Five per cent of the rate of irreversible loss of cystine arose from trans-sulfuration of methionine by ewes consuming the ration only, but greater percentages (14 and 22%) were observed when the ration was supplemented with SAA (P less than 0.05). These transfer quotients were not influenced by stage of pregnancy. The stage of pregnancy did not influence the concentration of cystine or methionine in the plasma, but the abomasal infusions of SAA significantly increased the concentration of both SAA. The ewes consuming the basal diet were in positive balance for both nitrogen and sulfur. The retention of nitrogen did not vary with stage of pregnancy (average (s.e.), 5.8 (0.9) g day-1), but that of sulfur increased from 0.6 to 1.0 and 1.3 g day-1 in periods 1, 2 and 3, respectively (P less than 0.05). The retentions of nitrogen (N, g day-1) and of sulfur (S, g day-1) were linearly and significantly related to the rate of infusion of organic sulfur into the abomasum (s, g day-1): N = 2.7 (+/- 0.7)s + 4.4 (+/- 0.3); and S = 0.49 (+/- 0.03)s + 0.72 (+/- 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Abomasum↗

Intracerebroventricular neuropeptide Y protects against stress-induced gastric erosion in the rat.

The effects of intracerebroventricular administration of neuropeptide Y (NPY) on stress-induced gastric erosion in the rat were investigated. Animals were exposed to water immersion stress after a single injection of 2 nmol NPY. Stress-induced erosion was reduced by approximately 50%. The plasma corticosterone levels were not affected. We interpret the protective effect of NPY as a manifestation of its sedative properties.

Animals↗

Intracerebroventricular neuropeptide Y suppresses open field and home cage activity in the rat.

Effects of intracerebroventricular administration of neuropeptide Y on open field behaviour, behavioural habituation and corticosterone response to open field testing, and on home cage activity have been investigated in the rat. In the open field, NPY reduced activity in a dose-dependent manner. Behavioural habituation was not influenced. After 5 days of recovery, NPY-treated animals did not differ from non-treated in any of the measured parameters. Peripheral corticosterone levels were not significantly affected, although there was a strong tendency towards an increase. Injection of 2 nmol NPY did not produce any gross neurological deficits. At this dose, NPY greatly suppressed home cage activity. The effect lasted throughout the recording period of 22 h, abolishing the normal circadian variation in activity. After 5 days of recovery, the effect was no longer present. Our interpretation of these findings is, that NPY is a highly potent endogenous agent capable of producing certain important aspects of behavioural sedation in a reversible manner. Since NPY did not decrease the corticosterone response to a novel stimulus, its pattern of actions seems to differ from synthetic sedative drugs.

Animals↗

Quality of poststressor rest influences the ulcerative process.

Gastric ulceration in rats is exacerbated by allowing a so-called recovery period after exposure to an ulcerogenic stressor. One hypothesis, which has support from pharmacological studies, argues that this effect is brought about by a rebound of parasympathetic activation. We tested this parasympathetic rebound hypothesis by presenting animals with a fear-inducing (sympathetic-activating) conditioned stimulus (CS) after 2 hr of water-restraint stress. Contrary to the hypothesis, presentation of such a CS increased severity of ulceration compared with those animals that did not receive the CS after restraint stress and control animals. These ulceration data favor instead a sustained activation hypothesis for ulceration, whereby presentation of the CS effectively prolonged the length of time during which animals were under stress, thus enhancing the degree of ulceration. Measurement of plasma corticosterone however indicated a negative correlation between adrenocortical activity and degree of gastric ulceration, contrary to that expected by a sustained activation hypothesis. It is suggested that this inconsistency may be because of the activating of a pituitary-endorphinogenic mediated stress analgesia.

Animals↗

Effect of central noradrenaline depletion on corticosterone levels and gastric ulcerations in rats.

Effects of central noradrenergic depletion on the stress responses of rats were explored using the new selective neurotoxin (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)). Noradrenergic depletion using DSP-4 was followed by a reduction in basal corticosterone levels after 7 days. Three weeks after DSP-4 treatment, animals exhibited less severe and fewer gastric ulcerations than control animals following 23 h immobilization stress, but stress levels of corticosterone were similar for the two groups. No differences could be found in the peripheral gastric levels of noradrenaline between experimental and control animals, while central noradrenaline was reduced to approximately 30% of control levels. The data support previous findings using other methods that central noradrenaline is an important factor in stress-induced gastric ulceration. The peripheral mechanisms for the protective effects of DSP-4 remain to be elucidated, and studies of these may cast light on the efferent pathways between the central nervous system and gastric mucosa which are involved in stress-induced gastric pathology.

Animals↗

Interactions amongst factors which influence severity of gastric ulceration in rats.

A number of factors have previously been demonstrated to influence the severity of stress-induced gastric ulceration in rats, including prior exposure to pre-shock and allowing animals a post-stress rest or recovery period. The primary purpose of this experiment was to investigate how one of these factors might modulate the expression of the other. Animals were pre-exposed to either signalled or unsignalled shock (using "learned helplessness" parameters), or no shock. They were later subjected to 2 hours restraint-in-water (immersion) stress, or appropriate handling control procedures. Half of the animals were sacrificed immediately on removal from the water-restraint, and half were sacrificed after a 2 hour recovery period in their home cages. Analysis of the severity and number of glandular stomach lesions indicated that animals subjected to the pre-shock exhibited greater ulceration than unshocked animals, as long as no post-stress rest period was allowed. Additionally, the effect of post-stress rest was masked by experience with pre-shock. This reciprocal modulation of treatment influences may offer suggestions for understanding discrepancies in the literature on the effects of these two modulating variables.

Animals↗