An acute stressor enhances sensitivity to a chemical irritant and increases51CrEDTA permeability of the colon in adult rats

We investigated the effect of prior acute stress on colonic permeability induced by a chemical irritant known to induce symptoms similar to inflammatory bowel disease in rodents. Adult male rats (n=12) were stressed by a single session of ten unpredictable, uncontrollable foot shocks, and half were home cage controls (n=12). Twenty-nine days later, half of each treatment group was exposed to 4% DSS (dextran sulphate sodium) solution in their drinking water for 48 hours while half received pure water over two periods separated by 17 days. After food deprivation overnight and light isoflurane anaesthesia the following morning, the animals were given a colonic infusion of 2000 nCi (nanocurie)⁵¹CrEDTA (⁵¹Cr-labelled ethylenediaminetetraacetic acid) and then placed individually in metabolic cages for a six hours continuous urine collection. Radioactivity in urine was measured by a gamma counter and percentage recovery of⁵¹CrEDTA calculated as an indicator of colonic mucosal permeability. Results concluded that pre-shocked animals exposed to DSS showed significantly higher mucosal permeability than the pre-shocked animals given water, and the non-shocked animals given either DSS or water. Pre-shock in combination with two exposures to a chemical irritant separated by 17 days had a pronounced effect on colonic permeability, indicating that stress should be considered a possible initiating or contributory factor to increased intestinal permeability related to a mucosal challenge.     

Psychological stress reactivates dextran sulfate sodium-induced chronic colitis in mice

Inflammatory bowel disease (IBD) is a chronic condition with alternating active and quiescent phases of inflammation. Stress has been suggested as a factor triggering a relapse of IBD. We investigated the role of repetitive psychological stress [water avoidance stress (WAS)] in reactivating colonic inflammation in a murine model of dextran sulfate sodium (DSS)-induced chronic colitis. Colitis was induced in C57BL/6 female mice by exposure to 3% DSS (5 days). During chronic inflammation(day 34), mice underwent repetitive WAS (1 h/day/7 days) and were given a sub-threshold concentration of DSS (1%, 5 days)or normal water to drink. At euthanasia (day 40), inflammatory parameters were assessed (colon inflammatory score, levels of inflammatory markers and histology). Mice with chronic colitis exposed to WAS had higher macroscopic and microscopic colonic inflammatory scores and levels of inflammatory markers (mainly IL-1beta, IL12p40 and CCL5) than non-stressed mice. Inflammatory responses were further enhanced by the presence of a sub-threshold concentration of DSS (1%). In mice without chronic inflammation, neither WAS nor 1% DSS, individually or in combination, elicited any inflammation. Hence stress, per se, reactivates a quiescent chronic inflammation, but does not initiate inflammation in healthy mice. Stress should be regarded as an environmental factor triggering IBD relapses in humans.     

Gastric ulceration and adrenocortical activity after inescapable and escapable pre-shock in rats

Two experiments are reported which investigated the effects of pre-shock treatment in rats on adrenocortical activity and susceptibility to later restraint-induced ulceration. In Experiment I, animals were exposed to a single inescapable 3 minute shock on 5 consecutive days. These shocked animals exhibited sensitisation of the adrenocortical response over days, increased adrenocortical reactivity to open field testing one week later and a trend for more severe ulceration after 20 hours of restraint. In Experiment II, animals were given 20 escapable or yoked pre-shock trials on 5 consecutive days. No sensitisation of the adrenocortical response was observed. Escape animals however were found to exhibit less gastric ulceration and a reduced adrenocortical responses after 20 hours of restraint 9 days after the last preshock session.     

Proactive sensitizing effects of acute stress on acoustic startle responses and experimentally induced colitis in rats: relationship to corticosterone

In humans, some individuals develop a syndrome after trauma (post-traumatic stress disorder, PTSD) characterized by increased startle responses and lower than normal cortisol secretion. We explored a rat model using the acoustic startle response (ASR) as a behavioral indicator of the effect of a short series of shocks. Because gastrointestinal disorders have been associated with prior stress, we also studied the rats' vulnerability to a chemically-induced colitis. After initial blood sampling, 12 rats were exposed to ten 1 mA 5 s foot-shocks while 12 rats served as controls. Nineteen days later the rats were tested for ASR. Thirty trials (10 trials at each of 95, 105, and 115 dB, pseudo-randomized) were given. After exposure for 6 days to dextran sulphate sodium in their drinking water, the rats were killed and the colons examined for erosions. Shocked rats showed greater startle responses and more colonic erosion than unshocked rats, but the shock effects were significant only for animals with low initial plasma corticosterone levels. Shocked rats also showed higher levels of granulocyte marker protein (GMP) in their faeces. These results suggest that low corticosterone secretion may represent a marker for vulnerability to long term effects of shocks as indicated by increased startle responses and colonic pathology.     

The residual spatial abilities of hippocampally lesioned rats can be enhanced by peripheral sympathetic-adrenal interventions

In order to test the possible effectiveness of peripheral interventions with the adrenergic system for the alleviation of certain disorders that typically follow bilateral hippocampal lesions, rats with bilateral lesions of the hippocampus, the overlying neocortex, or sham operations were tested at two postoperative times in the Morris water maze, a frequently used "spatial task." Half of the animals in all groups were exposed to the adrenergic manipulations, i.e., a chronic, 7-day, systemic bretylium regime (5 mg/kg) and, in addition, a peripheral injection of norepinephrine (4 micrograms/kg) 30 min before the start of each training day. The other half received saline chronically and a single saline injection before each training day. Five days of training were given at each of the two training periods. The first began 7 days after surgery while the second began 33 days after surgery. As expected, the hippocampally lesioned animals were severely impaired in the task. The adrenergic treatment produced enhanced performances in the rats with hippocampal lesions at both training sessions, although the improvement was greatest at the later period. Although the animals receiving the pharmacologic treatment located the general area of the hidden platform better than the saline-treated animals with hippocampal lesions, the treated animals were still impaired, swimming directly to the hidden platform on fewer trials than did animals in the other groups.     

Aggravation of DSS-induced colitis after chronic subordinate colony (CSC) housing is partially mediated by adrenal mechanisms

Chronic subordinate colony housing (CSC) is a relevant chronic psycho-social stressor for male mice. Here, we investigated effects of CSC on the severity of dextran sulphate sodium (DSS)-induced colitis and the involvement of adrenal mechanisms. After 19 days of CSC, male C57BL/6 mice were treated with 1% DSS (8 days). After 8 days, inflammatory shortening of the colon and the histological inflammation score were increased in CSC mice. Additionally, the increased secretion of pro-inflammatory cytokines by mesenteric lymph node cells found on day 2 and 4 of DSS treatment was down-regulated in CSC mice on day 8 of DSS treatment, paralleled by an increase in plasma corticosterone. In contrast, in unstressed controls, elevation of cytokine secretion was delayed and only found on day 8 of DSS treatment, associated with a prompt rise in plasma corticosterone. To reveal adrenal mechanisms in CSC-induced effects on colitis, mice were adrenalectomized, exposed to CSC and treated with DSS (8 days). In adrenalectomized CSC mice, the severity of DSS-induced colitis was reduced, as body weight loss, shortening of colon, histological damage score, and cytokine secretion from mesenteric lymph node cells were diminished compared with sham-operated CSC mice. In conclusion, exposure to chronic psycho-social stress increases the severity of acute DSS colitis, an effect which is, at least partly, mediated by adrenal mechanisms.     

Aversive potency of urine from dominant and subordinate male laboratory mice (Mus musculus): Resolution of a conflict

The present study assessed the aversive potency of urine collected from male albino mice that had been clearly identified as dominants/winners or subordinates/losers of paired aggression tests and then housed either individually or in a quasi-paired situation in which only a wire-mesh divider separated the two mice. This divider permitted constant visual, olfactory, auditory, and some tactile contact. The responses of individually tested, group-housed males were recorded when half of the substrate in a test box was treated with either water or one of the four urine types; the other half remained untreated. Significant preferences for the untreated half were found when the urine of winners or losers housed in individual metabolism cages or that of pair-housed dominants was used as the test stimulus. On the other hand, neither water nor the urine of cohabiting subordinate males was avoided. The present findings confirmed our earlier reports that the urine of dominant male mice was aversive, whereas that of their cohabiting subordinate partners was not. They also identified Sawyer's [1978] procedure of housing winners and losers in individual cages, with the consequent interruption of social contact as the likely reason for his failure to replicate our reports that subordinate male urine lacked aversive properties. The territorial implications of the aversive factor and other urinary signals are discussed.     

Learned helplessness in the cockroach (Periplaneta americana)

For 3 consecutive days cockroaches (Periplaneta americana) were exposed to either escapable, inescapable, or no shock in an escape task. Twenty-four hours later they were tested in a shuttlebox escape task. There were reliable differences between escapable and inescapable animals and between inescapable and control animals in both escape latencies and the number of failures to escape.     

Postnatal anoxia from CO2 for one minute produces sex-specific changes in contextual fear conditioning in adult rats.

In a split-litter design, equal numbers of male and female rats were exposed either to carbon dioxide for 1 min, or to the control condition on either postnatal Days 9-10 or 17-18. At 120 days of age half the numbers of rats in each condition were given subclinical dosages of lithium (1.5 mEq/kg) and pilocarpine (15 mg/kg) or saline. 40 days later all rats were tested in a conditioned fear paradigm. A four-way analysis of variance as a function of the variables anoxia, age at the time of anoxia sex, and subclinical seizure induction indicated a significant interaction between sex and anoxic history. Post hoc analysis showed that performance of male rats exposed to the anoxic condition did not differ from normal or anoxic female rats. The results suggest that only 1 min. of preweaning anoxia may produce permanent changes in contextual fear conditioning for male but not female rats.     

The role of pre-exposure to novel food tastes in activity-based conditioned taste avoidance

Rats were given differential exposure to three distinct and novel foods. One of these foods was exposed for 7 days; another for 2 days, and the last was not exposed. Next, half of the rats received six daily sessions in which a compound of the three flavors was followed by opportunities to run in wheels. The other rats received the food compound but without wheel running. On the next day, all rats were given a choice among the three food flavors presented concurrently in separate dishes. When the compound food had been followed by wheel running, rats ate little of the food given no pre-exposure, more of the food given 2 days of pre-exposure, and considerably more of the food given 7 days of pre-exposure. In comparison, rats who did not receive an opportunity to run ate equal and moderate amounts of the three foods. The results suggest that pre-exposure to a food’s taste produces latent inhibition that interferes with conditioned taste avoidance produced by pairing a taste (CS) with wheel running (US).     

Exchange of the hematopoietic system changes chemosensory identity

It has been shown that the scent of mice changes after a bone marrow transplantation. Previously obtained results were re-examined with a new design that rules out possible avoidance learning effects. Two BALB/c mice, deprived of water for 20 hours each day, were trained in a Y-maze to discriminate two fully allogeneic mice strains (C3H = S+ and C57 = S-) via their urine odor. Reinforcement for correct choice was provided by a drop of water. Urine samples of different fully allogeneic mice strains (C3H, C57 and A/J) and bone marrow transplanted chimeras (C57----C3H and C3H----C57) were submitted to different "transfer of training" -tests. In the conditioning paradigm used, the animals learn to identify S+ and also do not avoid S- after the training. The urine odor of the C57----C3H-chimeras was found to be different from the strain-specific urine odor of C3H animals. Since this change could not be found in syngeneic transplanted chimeras, it is concluded that it is caused by the graft. The experiments failed, however to demonstrate that the urine odor of allogeneic chimeras is constituted solely by donor- and recipient-specific components.     

Response persistence in the rat following intermittent punishment and partial reward: Effects of trial sequence

Thirty-six rats were given 16 days of partial reward training in a runway. During the final 12 days each of the animals received one foot-shock experience each day. One group received shock on an N trial preceding an R trial (P-R), a second group was shocked on N trials not followed by an R trial (R-P), and the third group received shock after completing all daily trials (Control). Following acquisition the rats were split within each group (one half received 24 trials of unpunished extinction and one half continued to receive partial reward but were punished on every trial). During consistent punishment the P-R animals were more persistent than the R-P or Control rats and during unpunished extinction the P-R and Control animals were equal in persistence but both were superior to the R-P animals. The results were discussed in terms of Capaldi's sequential trial theory.     

Enrichment versus exercise effects on motor impairments following cortical removals in rats

Groups of rats were exposed to an enriched environment, given access to an activity wheel, or individually housed in wire mesh cages, impoverished. Rats were exposed in groups of four to the enriched environment or placed individually in the activity wheel for 2 h per day for 25 days preoperatively. Within each exposure group, rats sustained bilateral removals of sensorimotor cortex, or were sham-operated controls. Animals were trained preoperatively to locomote across a narrow elevated runway. Postoperatively, locomotor testing was initiated 17 days after surgery throughout which time all animals were maintained under impoverished conditions. Locomotor deficits following cortical damage were a function of preoperative exposure: enriched rats were least impaired; impoverished rats were most impaired. Rats allowed running wheel activity initially showed the same marked deficits as impoverished animals but recovered more rapidly. The opportunity for physical exercise afforded wheel animals preoperatively may have enhanced motor capabilities that aided recovery. However, physical activity alone did not yield the same protective effects from initial impairment as enrichment. Greater elaboration of neural structures associated with perceptual-motor enrichment probably accounted for the initial sparing of the enriched group.     

Achievement motivation in relation to achievement-related recall,performance, and urine flow,a marker associated with release of vasopressin

Administration of the pituitary hormone, arginine vasopressin (AVP), enhances memory in animals and humans. Since AVP is the antidiuretic hormone, its release can be inferred from reductions in urine flow. Forty-six male adults recalled the contents of a complex story and then either were exposed to achievement arousal or were not. Significantly more of the subjects in the aroused than the nonaroused condition showed a decrease in urine flow, and the greater the decrease in urine flow among the achievement-aroused subjects, the better the recall of achievement-related story content 24 hours later. Subjects high inn Achievement, in the achievement-oriented condition, showed lower urine output at the outset of the second day and greater improvement in learning to unscramble words. Since lower urine output was also related to improvement in unscrambling words, achievement arousal may have released AVP which in turn may have facilitated achievement-related retention and performance.I am greatly indebted to Sean Connelly for assistance in carrying out this research and to Dr. Franklin Epstein of the Beth Israel Hospital, Boston, for helping me to understand how the kidney functions in producing urine.     

Interval, blocking, and marking effects during the development of schedule-induced drinking in rats

Schedule-induced drinking (SID) can occur when food-deprived rats are given access to water while receiving pellets on an intermittent reinforcement schedule. These conditions can increase water intake excessively. The possible role of adventitious reinforcement of postpellet drinking was assessed by testing whether response-reinforcer contiguity, the relative predictiveness of a response, and whether it is marked are important in the development of SID. Rats exposed to a short interpellet interval acquired SID most rapidly, with this acquired drinking response maintained when animals were transferred to a longer interpellet interval, thus indicating an easy-to-hard effect (Experiment 1). Further experiments demonstrated that a stimulus (a brief-flashing house light) occurring prior to pellet delivery could block the acquisition of SID (Experiment 2), while a lick-contingent tone, intended to increase the associability of this response, produced more rapid acquisition of SID (Experiment 3). Analysis of lick distributions revealed that licking became concentrated in the first half of an interpellet interval only after several sessions. Overall, the results indicated that similar factors affect the acquisition of both SID and instrumental conditioning with delayed reinforcement, as is consistent with a superstitious conditioning account of SID development.     

Effects of BIM-22015, an analog of ACTH4-10, on functional recovery after frontal cortex injury.

Male rats, 90-100 days old, with frontal cortex lesions were given either subcutaneous sterile water (SW) as a vehicle control or 1, 10, or 100 micrograms of BIM-22015 every other day for 20 days. Brain-injured subjects tested in the Morris water maze with either 10 micrograms BIM-22015 or SW took significantly more trials than sham-operated rats to locate a submerged platform eight consecutive times within 60 s. The animals given 1 or 100 micrograms BIM-22015 took significantly fewer trials to reach criterion than brain-injured animals in the other drug treatment groups. On a percentage of savings, measured 8 days after reaching criterion, the brain-injured subjects given 1, 10, or 100 micrograms BIM-22015 did not differ from sham-operated rats. In contrast, the brain-injured animals given SW took longer to find the submerged platform than they did during the initial training. To assess long-term effects of the ACTH analog treatment, rats were trained on a delayed spatial alternation task 30 days after receiving the last injection. On this task, brain-injured rats treated with the 10-micrograms dose performed significantly better than those given sterile water. Acetylcholinesterase (AChE)-labeled neurons counted in the nucleus basalis magnocellularis indicated that rats with frontal cortex damage given the 10-micrograms treatment did not differ from the sham controls and had significantly more AChE-positive neurons than injured counterparts treated with SW or 100 micrograms.     

Odor-aversion learning and retention span in neonatal mouse pups

One hundred and sixty-four litters of Swiss CD-1 random-bred mice were used to assess learning and retention capacities during the first postnatal week. In Experiment 1, whole 7-day litters were exposed for 65 min to commercial extracts of either mint or lemon sprinkled over wood shavings. Five minutes after the beginning of the exposure, half of the litters were injected ip with the illness-inducing agent lithium chloride (LiCl; 0.20 M, 2% of body weight); the other half was treated with saline solution (8% NaCl). On Postnatal Day 10, the animals were singly introduced in a warmed arena for a 180-s preference test, and the time spent in the mint- and lemon-scented areas of the apparatus was recorded. When compared with saline-injected pups, mice that experienced lemon-LiCl pairings showed a significant aversion for the lemon-scented area, while the mint aversion in the mint-LiCl group just missed statistical significance. Three additional control groups (unhandled on Day 7, or only LiCl- or saline-injected) did not show significant preferences for either the mint or the lemon odor. In Experiment 2, litters of 3, 5, or 7 days were similarly exposed to lemon-scented shavings for either 5 or 20 min, injected with LiCl or saline, and then exposed for an additional 60 min to the shavings. On Postnatal Day 10, tests like those of Experiment 1 showed a significant odor-aversion in animals conditioned on Day 7, but not in those conditioned on Day 3 or 5. In Experiment 3, 3- and 5-day old pups were exposed to lemon odor-LiCl or -NaCl pairings, and tested for aversion after 3 or 7 days (CS duration 5 min before injection and either 30 or 60 min after injection). Only when the conditioning-testing interval was limited to 3 days did LiCl-injected groups show a significant aversion, which did not depend on duration of CS exposure.     

A study of the effets of restraint stress on colitis induced by dextran sulphate sodium in singly housed rats

The inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) are multifactorial diseases. Clinical reports indicate that emotional stress may contribute to the onset, progression and remission of these diseases. Using an experimental animal model of ulcerative colitis, the effect of stress on the development of and recovery from symptoms, was studied prospectively. Singly housed rats received 4 percent dextran sulphate sodium orally until, fecal blood was detected, indicating the presence of colonic erosions. Tap water was then administered until there were no signs of fecal blood. Two hours of restraint stress were administered daily over four successive days, either prior to or after the induction of colitis. Latencies in days to symptom development and recovery were compared to an unstressed, group. Daily measures of fluid-intake, body-weight, and hemoglobulin in feces were made. Results  Rats exposed to restraint stress procedures prior to induction of colitis had shorter latencies to development of symptoms. There was no significant difference in latency to recovery. The amount of fluid-intake did not significantly differ between groups, nor did the groups differ in body-weight. Conclusion  There is an effect of stress on the latency to develop colitis induced by dextran sulphate sodium. This preliminary study suggests that the impact of stress may be one factor underlying the emergence of ulcerative colitis.     

东莨菪碱对吗啡诱导的大鼠行为敏感化的影响

药物重复处理导致的行为敏感化与成瘾过程密切相关。本实验检验东莨菪碱对吗啡诱导的大鼠行为敏感化发展和转化的影响。实验一动物分为3组,分别进行生理盐水（对照组）、吗啡（10mg/kg,吗啡组）、吗啡（10mg/kg）＋东莨菪碱（3mg/kg,吗啡-东莨菪碱组）前处理,36小时腹腔注射4次（第1~2天）。自然戒断7天（第3~9天）。第10天,所有动物均使用吗啡（4mg/kg）激发,记录动物的自发活动量;第24天,吗啡组和吗啡-东莨菪碱组动物重复第10天的操作。实验二动物分为3组,分别接受生理盐水（对照组）、吗啡（10mg/kg,吗啡组）、吗啡（10mg/kg,吗啡-东莨菪碱组）处理,36小时腹腔注射4次（第1~3天）;间隔12小时后,3组动物分别接受生理盐水、生理盐水和东莨菪碱（3mg/kg）处理,仍为36小时腹腔注射4次（第3 ~5天）。第6~9天不进行药物处理。第10天和第17天,分别使用吗啡（4mg/kg）激发,记录动物的活动量。记录时间均为两小时(10分钟为一个记录单元)。结果表明,东莨菪碱能够抑制吗啡诱导的行为敏感化的发展,一定程度上也能够延缓行为敏感化的转化但没有阻断这种转化     

Substance P facilitation of memory: effects in an appetitively motivated learning task

Food deprived, heterogeneous strain (HS/IBG) mice were trained on two different discrimination tasks for food reinforcement. In one experiment animals were trained to make spatial discriminations in a T maze. Immediately after training they were given subcutaneous injections of either substance P (1 ng/g) or vehicle. Twenty-four hours later the animals were given reversal training in the same maze. The results showed that substance P-treated animals took significantly longer to acquire the reversal habit than did control mice. In a second experiment, animals were trained to make visual discriminations in a T maze. Immediately after reaching acquisition criterion animals were injected with either substance P (1 ng/g) or vehicle. Different groups of mice were retrained on the same task either 1, 2, 3, or 7 days after original learning. Savings scores were calculated and, at every interval, substance P-treated mice retained the task better than control animals. One interpretation of these data is that substance P-treated mice remembered the original task significantly better than vehicle-injected control animals.