PubMed Health⌕ Search

Biomedical subjects

R Stam

Publications and source records attributed to R Stam.

At least 19 recordsLinked to original sources
PubMed2005

Altered brain stem responsivity to duodenal pain after a single stressful experience.

A single session of foot shock stress produces stable and long lasting sensitization of behavioral, hormonal and intestinal motility responses to novel stressful stimuli in laboratory rats. This is reflected in increased expression of the activity marker protein Fos in brain areas involved, following an external stressor. We present data from awake, freely moving rats in which a silicone balloon was surgically implanted in the duodenum. Firstly, cardiovascular reflexes to distentions were studied using telemetry with surgically implanted transmitters, 2 weeks after a single, 15-min session of foot shocks. The distentions caused characteristic, bi-phasic responses in both mean arterial blood pressure and heart rate that were not different between preshocked and control animals. Secondly, the numbers of Fos immunopositive cells were quantified in selected brain areas, 1 h after repeated distention of the duodenum. We found an increase in distention-induced Fos in preshocked rats in the nucleus tractus solitarius and a weaker effect in the central nucleus of the amygdala. This could be a first indication that altered visceral afferent processing in previously stressed rats, found earlier for the colon, may be a general and not an organ-specific phenomenon.

Adaptation, Physiological↗
PubMed2001

LY354740 attenuates the expression of long-term behavioral sensitization induced by a single session of foot shocks.

Exposure of rats to a single session of foot shocks sensitizes behavioral responses to novel stimuli. There is evidence that metabotropic glutamate (mGlu) receptors play a role in sensitization processes. In the present study, we investigated the role of mGlu(2/3) receptors in the long-term (14 days) increase in defensive withdrawal behavior after a single session of foot shocks. Exposure to foot shocks increased defensive withdrawal behavior. The mGlu(2/3) receptor agonist LY354740 ((1S,2S,5R,6S)-(+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 0.1 mg/kg, i.p.) normalized the increased latency and the decreased time in the light of the preshocked rats. We conclude that activation of mGlu(2/3) receptors attenuates the foot shock-induced expression of behavioral sensitization.

Animals↗
PubMed2001

Stress-induced sensitization of CRH-ir but not P-CREB-ir responsivity in the rat central nervous system.

There is some evidence that a traumatic life event can induce long-term alterations in corticotropin-releasing hormone (CRH) producing neurons in humans, which may play a role in the pathophysiology of anxiety disorders, including post-traumatic stress disorder (PTSD). To study the long-term effects of a traumatic event on brain CRH-immunoreactivity (CRH-ir) and phospho-cAMP response element binding protein-immunoreactivity (P-CREB-ir), rats were exposed to a single session of foot shocks (preshocked) or no shocks (control). Two weeks later half of the control rats and half of the preshocked rats received an electrified prod in the home cage for 15 min and behavior was recorded. Fifteen minutes after the removal of the prod rats were perfused and brain sections were stained for CRH-ir and P-CREB-ir. There was no basal difference between preshocked and control rats in brain CRH-ir and P-CREB-ir. Exposure to the electrified prod induced a significant increase in CRH-ir in the paraventricular nucleus of the hypothalamus, the median eminence and the central amygdala in preshocked rats, but not in control rats. The electrified prod increased the number of P-CREB-ir neurons in the paraventricular nucleus of the hypothalamus and the locus coeruleus, but the preshock experience did not affect this response. In an additional experiment with a similar design plasma hormone levels were measured 14 days after the foot shocks. The preshock experience sensitized the shock prod-induced ACTH and corticosterone response. No behavioral differences between preshocked and control rats were found during the shock prod tests. We suggest that long-term stress-induced changes in neuropeptide dynamics of CRH-ir neurons may play a role in long-term stress-induced neuroendocrine sensitization.

Adrenocorticotropic Hormone↗
PubMed2001

Effect of a benzodiazepine receptor agonist and corticotropin-releasing hormone receptor antagonists on long-term foot-shock-induced increase in defensive withdrawal behavior.

RATIONALE: Traumatic life events can induce long-term alterations in neuronal substrates, which may ultimately lead to the development of anxiety disorders. It has been postulated that corticotropin-releasing hormone (CRH) plays an important role in anxiety-like behavior. OBJECTIVES: (1) To study the long-term effects of a single foot-shock experience on defensive withdrawal (DW) behavior in rats. (2) To examine the effects of the benzodiazepine anxiolytic drug chlordiazepoxide on the behavior of preshocked and control rats in the DW test. (3) To study the role of endogenous CRH in the long-term stress-induced increase in DW behavior. METHODS: (1) Rats were exposed to a single session of foot shocks or exposed to the grid cage without receiving any shocks. Two, six and ten weeks later, rats were tested in the DW tests (2, 3). In subsequent experiments, rats were exposed to foot shocks or exposed to the grid cage without receiving any shocks, and 2 weeks later the effect of pharmacological treatments on the behavioral response in the DW test was investigated. Chlordiazepoxide (1, 5, 10 mg/kg BW, i.p.) and the CRH antagonists D-Phe CRH(12-41) (0.2, 1, 5 microg per rat, i.c.v.) and alpha-helical CRH(9-41) (5 microg per rat, i.c.v.) were injected 30 min before the test. RESULTS: A single session of foot shocks induced a long-term increase in DW behavior, which persisted after repeated testing for at least 10 weeks. Chlordiazepoxide decreased the latency but did not affect time spent in light, distance moved, or the number of entries in the open field. D-Phe CRH(12-41) had no behavioral effects. alpha-Helical CRH(9-41) increased the time spent outside the box, primarily as a result of effects of alpha-helical CRH(9-41) in controls. CONCLUSION: These data demonstrate that preshocked rats display long-term increased anxiety-like behavior in the DW test but that CRH is unlikely to be involved in its expression.

Animals↗
PubMed2001

Long-term sensitization of cardiovascular stress responses after a single stressful experience.

There is evidence that the experience of traumatic events may play a role in the pathogenesis of somatic diseases, including cardiovascular disorders. In this study, telemetry was used to investigate the long-term effects of a single stressful experience on cardiovascular and behavioral responses to novel challenges 2 weeks later. Rats were exposed to footshocks and tested for sensitization using the following challenges: novel cylinder (Day 14); shock prod acquisition test (Day 15); and shock prod retention test (Day 16). No difference in basal somatomotor activity (SA), heart rate (HR) and blood pressure between preshocked rats and control rats was found. However, preshocked rats displayed an enhanced blood pressure response compared to controls during the shock prod acquisition test and the shock prod retention test. No differential increase in HR response between both groups was found. During the novel cylinder test, the preshocked rats displayed less SA while no behavioral differences were found in the shock prod acquisition test and the shock prod retention test. We conclude that a single stressful experience induces long-term sensitization of blood pressure responses to novel challenges that are not necessarily linked to sensitized behavioral responses. The footshock model may be a useful model to study autonomic hyperresponsivity found in posttraumatic stress disorder (PTSD).

Animals↗
PubMed2000

Long-lasting stress sensitisation.

Stressful experiences in humans can result in a spectrum of long-term changes in behavioural, autonomic and hormonal responsivity. An extreme form of such alterations is found in patients with post-traumatic stress disorder (PTSD). A number of animal models has been developed in which intense stressful experiences (shocks, social confrontations) result in longterm altered responsivity of behavioural, autonomic and hormonal responses to aversive challenges which mimic many of the changes seen in PTSD. These models of stress-induced sensitisation are beginning to generate a better understanding of the vulnerability factors, time-course and underlying neuronal substrates of the long-term disturbances experienced by humans as a result of stressful life events.

Animals↗
PubMed2000

Endogenous corticotropin-releasing hormone inhibits conditioned-fear-induced vagal activation in the rat.

The role of the endogenous corticotropin-releasing hormone (CRH) system in the regulation of heart rate, PQ interval (a measure of vagal activity), gross activity and release of adrenocorticotropic hormone (ACTH), noradrenaline and adrenaline into the blood during conditioned fear was studied in freely moving rats. Intracerebroventricular (i.c.v.) infusion of alpha-helical CRH-(9-41) (10 microgram/3 microliter), a non-selective CRH receptor antagonist, under resting conditions had no significant effect on gross activity, heart rate and PQ interval, indicating that alpha-helical CRH at this dose was devoid of agonist effects. Conditioned fear was induced by 10 min forced exposure to a cage in which the rat had experienced footshocks (5x0.5 mAx3 s) 1 day before. Conditioned-fear rats showed freezing behaviour, associated with an increase in heart rate, PQ interval, noradrenaline and adrenaline, indicating that the conditioned-fear-induced cardiac effects were the result of coactivation of the sympathetic and parasympathetic nervous system. The i.c.v. pre-treatment of rats with alpha-helical CRH significantly reduced the conditioned-fear-induced tachycardiac and ACTH response, and enhanced the increase in PQ interval, without affecting the noradrenaline and adrenaline response. These results suggest that endogenous CRH reduces the vagal response to conditioned-fear stress in rats. To test this, rats were pre-treated with atropine methyl nitrate (0.3 mg/kg, subcutaneously; s.c.), a peripherally acting cholinergic receptor antagonist. This resulted in a complete blockade of the alpha-helical CRH-induced decrease in heart rate response and increase in PQ interval. From these findings, it is concluded that endogenous CRH in the brain inhibits vagal outflow induced by emotional stress.

Adrenocorticotropic Hormone↗
PubMed2000

The role of the CRH type 1 receptor in autonomic responses to corticotropin- releasing hormone in the rat.

The involvement of the corticotropin-releasing hormone (CRH) type 1 receptor in CRH-induced cardiac responses was studied in freely moving rats. Intracerebroventricular (icv) infusion of 2 microg CRH under resting conditions resulted in a significant increase in heart rate (HR), but did not significantly affect the PQ interval of the electrocardiogram. This effect involves sympathetic nervous system (SNS) activation, since CRH-treatment resulted in a marked increase in plasma norepinephrine (NE) and epinephrine (E), and sympathetic blockade by subcutaneously injected atenolol (1 mg/kg), a beta1-selective adrenergic antagonist, completely prevented the CRH-induced tachycardia. CRH infusion after sympathetic blockade resulted in an elongation of the PQ interval, indicating CRH-induced vagal activation. Gross locomotor activity (GA) was determined to study its possible indirect effects on cardiac activity. Although CRH induced a marked increase in GA, this effect followed the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but was a direct effect of icv CRH. Treatment with CP-154,526 (icv, 10 or 25 microg), a selective CRH type 1 receptor antagonist, did not affect baseline HR, plasma NE and E, whereas it partially blocked the CRH-induced increase in HR, plasma NE and E levels. CP-154,526 treatment had no significant effects on baseline or CRH-induced changes in GA. These results indicate that CRH activates the sympathetic nervous system at least in part via the CRH type 1 receptor.

Adrenergic beta-Antagonists↗
PubMed1999

Long-term sensitization of Fos-responsivity in the rat central nervous system after a single stressful experience.

There is considerable evidence for a role of stressful experiences in psychosomatic disorders in humans, but the mechanisms leading to altered responsivity and the relative contributions of central and peripheral neuronal changes, however, are still under debate. To investigate the contribution of specific brain areas to sensitized responsivity, rats were exposed to a single brief session of inescapable footshocks (preshocked) or no shocks (control) in a gridcage. Two weeks later, an electrified prod was inserted in the home cage for 15 min and the behaviour recorded. One hour later rats were perfused and brain sections were stained for Fos protein immunoreactivity. The number of Fos positive neurons was quantified in 27 brain areas. No significant difference in behaviour was found between the groups during the shock prod challenge. A significantly higher number of Fos positive neurons was found in preshocked rats compared to controls in the following brain areas: agranular insular cortex, frontal cortex, nucleus accumbens, bed nucleus of the stria terminalis, basolateral amygdala, CA1 area of the hippocampus, paraventricular hypothalamic nucleus, dorsolateral central grey, locus coeruleus, nucleus of the solitary tract and lateral paragigantocellular nucleus. We conclude that altered reactivity to stressful challenges in brain areas involved in neuroendocrine and autonomic control may play a role in long-term sensitization of neuroendocrine and autonomic responses in preshocked rats under conditions where behavioural sensitization is not expressed.

Animals↗
PubMed1999

Sex differences in long-term stress-induced colonic, behavioural and hormonal disturbances.

Functional bowel disorders are more prevalent in women than in men, but the reason for this is unclear. Stressful experiences can increase the risk for or precipitate intestinal dysfunction. Using a model for long-term stress-induced sensitisation in rats, it was investigated whether male and female rats differ in susceptibility for long-term colonic, behavioural and hormonal disturbances following brief but intense stress. Male and female Wistar rats were fitted with chronic electrodes on proximal colon and given either a 15-minute session of foot shocks or no shocks. Two weeks later, rats were exposed to two different novel stressful challenges in the home cage: an electrified prod (day 14) and an 85 dB noise stressor (day 15). Digitalised colonic myoelectric spike burst activity was quantified automatically. Behaviour during prod and noise exposure was scored blindly from videotape. Resting plasma hormone concentrations at the end of the study were determined by radio-immuno assay. Following prod stress on day 14, both male and female preshocked rats showed a greater increase in colonic spike burst frequency than controls, but similar behaviour, and the dynamics of colonic motility differed between sexes. Following noise stress on day 15, only a small change in burst frequency was seen in all rats, but preshocked rats showed less self-grooming behaviour and there was a tendency for preshocked females to show increased noise-induced immobility. Preshocked rats also had lower levels of plasma free thyroxine. While both male and female rats show long-term stress-induced colonic sensitisation and hormonal changes, females show a different activation pattern of colonic motility, and may be more vulnerable for altered behavioural reactivity, following stress.

Adrenocorticotropic Hormone↗
PubMed1998

Conditioned fear-induced tachycardia in the rat: vagal involvement.

The effects of conditioned fear on gross activity, heart rate, PQ interval, noradrenaline and adrenaline were studied in freely moving rats. Subcutaneous (s.c.) injections of atropine methyl nitrate (0.5 mg/kg) during rest resulted in a significant shortening of the PQ interval, indicating that the PQ interval can be used as a measure of vagal activity. Conditioned fear was induced by 10-min forced exposure to a cage in which the rat had previously experienced footshocks (5 x 0.5 mA x 3 s). In non-shocked controls, an increase in gross activity was found and a pronounced tachycardia, without changes in PQ interval. Conditioned fear rats showed immobility behaviour, associated with a less pronounced tachycardia and an increase in PQ interval. Noradrenaline was similarly increased in both groups, whereas adrenaline was increased in conditioned fear rats only. To further evaluate the role of the vagus, rats were exposed to conditioned fear after pre-treatment with atropine methyl nitrate (0.5 mg/kg, s.c.). Again, immobility was observed with a concomitant tachycardia, but without an increase in PQ interval. These results indicate that the autonomic nervous system is differentially involved in heart rate regulation in conditioned fear rats and in non-shocked controls: in non-shocked controls a predominant sympathetic nervous system activation results in an increase in heart rate, whereas in conditioned fear rats the tachycardiac response is attenuated by a simultaneous activation of sympathetic nervous system and parasympathetic nervous system.

Animals↗
PubMed1997

Behavioural and intestinal responses to novelty in rats selected for diverging reactivity in the open field test.

There are indications that the severity of functional gastrointestinal disturbances in humans is linked to individual coping styles. In rodents, the open field test can be used to assess individual differences in behavioural responsivity to novel challenges. Two groups of Wistar rats were selected for high (HA) and low (LA) locomotor activity in a novel open field and fitted with electrodes on the proximal colon. During subsequent exposure to a novel box, a smaller locomotor activation in LA was accompanied by a greater increase in colonic spike burst activity compared to HA rats, even though this novel stressful challenge did not result in a clear defecation response in either group. In contrast, no marked behavioural differences between HA and LA were seen in the shock prod paradigm. Although detection of divergent behavioural responsivity in HA and LA rats may depend on stimulus quality or intensity, combined use of behavioural selection and intestinal motility recording in freely moving rats may offer a model to study individual vulnerability to stress-related disturbances of intestinal function.

Action Potentials↗
PubMed1996

Sensitization of the colonic response to novel stress after previous stressful experience.

Stressful life events may be important causative or precipitating factors for functional gastrointestinal disorders such as the irritable bowel syndrome in humans. In the rat, a single session of foot shocks is known to sensitize the behavioral and hormonal responses to subsequent stress, but intestinal responses have not been investigated. Rats were fitted with bipolar electrodes on proximal colon and exposed to a single session of foot shocks (10 x 6 s in 15 min; preshocked) or no shocks (control). Weight gain after foot shocks was identical to that in controls. Two weeks after foot shocks, basal colonic spike burst frequency did not differ from controls or from that recorded before shock treatment. Unlike controls, however, preshocked rats showed a significant increase in colonic spike burst frequency to a novel stressful challenge in the home cage, an electrified prod. Because the behavioral responses to this challenge did not differ, colonic hyperresponsiveness in preshocked rats may represent a form of stress-induced autonomic sensitization. The model should be a useful tool to study mechanisms and pharmacotherapeutic approaches of the gastrointestinal consequences of traumatic stress.

Animals↗
PubMed1995

Effects of novelty and conditioned fear on small intestinal and colonic motility and behaviour in the rat.

Novelty and conditioned fear were used to investigate the effects of psychological stress on fasting small intestinal and colonic myoelectric activity and their relation with behaviour in freely moving rats fitted with bipolar electrodes on proximal jejunum and colon. Rats in both novelty and conditioned fear groups spent a 15 min session in a novel box, where only rats in the fear group received unescapable, repeated foot shock (10 x 6 s, 0.5 mA). Behaviour in groups reexposed to the box on day 1 or day 7 indicated a profound difference in emotional state. Conditioned fear rats remained largely immobile, while novelty rats displayed active exploratory behaviour. Behaviour during conditioned fear did not differ significantly between rats reexposed to the box either 1 or 7 days after foot shock, while novelty animals appeared more aroused on day 7. Conditioned fear on day 1 caused a significant increase in colonic spike burst frequency compared to basal values in the home cage. A smaller but significant increase was found in novelty rats. In groups tested after 7 days, both novelty and conditioned fear resulted in small increases in colonic burst frequency that did not differ significantly from each other. No effects were found on the incidence of the fasting jejunal Migrating Motility Complex. Defecation was see only in conditioned fear rats, but did not differ quantitatively between day 1 and day 7. We conclude that, in the rat, colonic myoelectric spike burst activity is highly responsive to psychological stress, while the fasting pattern of small intestinal activity is more resistant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Computer analysis of the migrating motility complex of the small intestine recorded in freely moving rats.

Myoelectric activity of the small intestine was recorded digitally in fasted, freely moving rats fitted with multiple pairs of electrodes in the antimesenterial smooth muscle. The electrodes were implanted under strict aseptic conditions to safeguard the animal's health and thereby benefit experimental results. As in many other mammalian species, the fasted electrical and mechanical activity of the small intestine in the rat consists of alternating periods of activity and quiescence jointly called the Migrating Motility Complex (MMC). Existing methods for the analysis of small bowel myoelectric activity either integrate spike activity over longer periods of time or describe characteristics of single bursts. We have developed a computer program for fast, automated analysis that distinguishes the three characteristic phases of the MMC. The computer program recognizes periods of varying spike burst frequency and then produces a graphical and numerical output of the length and mean burst frequency of the different phases of each MMC that correlates well with the results of visual evaluation. The techniques used are discussed in relation to existing recording and analysis methods, and specific decisions in the program are motivated. The system will be a useful tool in assessing the effects of drugs, peptides, or stress on small bowel motility.

Animals↗
PubMed1993

The expression of GAP-43 mRNA in developing embryonic striatal tissue grafts.

We have studied by quantitative in situ hybridization histochemistry the mRNA expression of the growth associated phosphoprotein (GAP-43) in grafts of foetal striatal neurones implanted into the ibotenic acid lesioned adult rat neostriatum. Animals were studied at 7, 15, 30 and 90 days after implantation. Using a 35S-labelled specific oligonucleotide probe we observed the highest levels of GAP-43 mRNA in 15-day-old grafts; levels were significantly reduced at 30 days and in 3-month-old grafts GAP-43 mRNA expression was not significantly different from the very low levels in the normal rat striatum. The data indicate that GAP-43 mRNA is highly expressed in developing but not mature neurones and suggest that embryonic striatal grafts may develop a relatively adult phenotype within the host brain by about 4 weeks; by which time most of the synaptic connections are established.

Animals↗