Biomedical subjects

V M Wiegant

Publications and source records attributed to V M Wiegant.

At least 19 recordsLinked to original sources

PubMed2003

Short- and long-term effects of neonatal glucocorticoid therapy: is hydrocortisone an alternative to dexamethasone?

AIM: To compare short-term effects and neurodevelopmental outcome of neonatal glucocorticoid therapy between two centres. METHODS: A retrospective study was performed in two centres using a tapering course of either 5 to 1 mg kg(-1) hydrocortisone (HC; 22 d) or 0.5 to 0.1 mg kg(-1) dexamethasone (DEX; 21 d). In both centres glucocorticoid-treated infants and control patients were matched for gestational age, birthweight, severity of infant respiratory distress syndrome and periventricular-intraventricular haemorrhage. The following short-term glucocorticoid-induced effects were investigated in 25 HC-treated and 25 control patients in centre A, and in 23 DEX-treated and 23 control patients in centre B: oxygen dependency (inspiratory oxygen fraction), arterial pressure, blood glucose and urea concentrations, weight gain and head circumference before, during and after therapy (in treated infants), or at an interval comparable to treated infants (in control infants). Neurological outcome, psychomotor development and school performance at 5-7 y of age was evaluated in all groups. RESULTS: HC and DEX were equally potent in reducing oxygen dependency. Mean arterial pressure as well as blood glucose and urea concentrations were significantly increased during DEX, but not during HC treatment. Weight gain stopped during DEX therapy, but not during HC. Head circumference in both treatment groups was decreased after therapy compared with controls. Neonatally DEX-treated children needed special school education significantly more often (p < 0.01) than controls at 5-7 y of age. No differences between neonatally HC-treated children and controls on neurodevelopmental outcome were found at 5-7 y of age. CONCLUSION: Neonatal HC therapy has fewer short- and long-term adverse effects than neonatal DEX therapy.

Anti-Inflammatory Agents↗

PubMed2002

Opioid activity in behavioral and heart rate responses of tethered pigs to acute stress.

In a longitudinal experiment, effects of long-term tether housing on heart rate and behavioral responses to an acute stressor (a 15-min challenge with a nosesling) were investigated in pigs. The animals were challenged during loose housing and again after 10-11 weeks of tether housing. To detect possible changes in endogenous opioid systems modifying these responses, the pigs were pretreated with the opioid receptor antagonist naloxone (0.5 mg/kg body weight, iv). In response to the nosesling challenge, the animals showed pronounced resistance behavior and a sharp rise in heart rate. Following this initial phase of resistance, the heart rate dropped to prechallenge levels or below this line, and the pigs seemed to become sedated. Pretreatment with naloxone increased the heart rate response in animals that were long-term tether housed (n=12). No such effect was found in the control group (n=5) that was loose-housed during the entire experiment, indicating that the impact of endogenous opioid systems mitigating heart rate responses to acute stress had increased as a result of long-term tether housing. Changes in the effect of naloxone on the behavioral response were not found. Adaptive changes in opioid systems may prevent excessive physiological reactions to acute stress and, thus, may serve as a coping mechanism.

Animals↗

PubMed2002

Brain opioid receptor density reflects behavioral and heart rate responses in pigs.

Results from our previous research indicate that long-term tether-housed pigs with high and low levels of stereotypies show differences in the density of endogenous opioid receptors in the hippocampus and hypothalamus. It was not clear whether differences in opioid receptor density were induced by the chronic stress of tether housing or stereotypy performance, or were already present before the animals were tethered. The latter possibility was tested in the present experiment. We used a group of 18 nonstereotyping pigs that had no experience with tether housing and investigated whether the animals differed in the density of endogenous opioid receptors in the brain and, if so, whether these differences were related to the animals' reactions to acute challenges. The pigs were subjected to two tests: an open field test and a tethering test. Behavioral reactions as well as heart rate responses were measured. Opioid receptor densities were determined postmortem in the hippocampus and hypothalamus using a membrane binding assay with [(3)H]naloxone as a ligand. Animals differed widely in their responses to the two tests. In support of our hypothesis, we found a relationship between behavioral and heart rate responses and densities of naloxone binding sites in the hippocampus and hypothalamus. The data suggest that endogenous opioid systems in the brain contribute to differences in stress responding between individual pigs.

Adaptation, Psychological↗

PubMed2002

Individual differences in behavioral and physiological responses to restraint stress in pigs.

Several recent studies on pigs have demonstrated a relationship between the degree of resistance displayed early in life in a so-called backtest and a variety of behavioural and physiological responses in piglets and young fattening pigs. To study whether pigs with diverging responses in the backtest, i.e., high-resisting (HR) and low-resisting (LR) pigs, differ also in adulthood in their responses to an acute stressor, adult nulliparous HR (n=36) and LR gilts (n=36) housed in groups or stalls were challenged by 5-min fixation with a nose sling. During the first minute of restraint, HR gilts vocalised significantly more than LR gilts. Over the whole 5-min period, HR gilts tended to vocalise more than LR gilts. Housing or backtest type did not affect immediate cortisol increase (Delta(-5 min; 15 min)). At t=45 min, cortisol concentrations in HR gilts but not in LR gilts were still higher than at t=-5 min. Heart rate quickly decreased during the first min of restraint and remained fairly constant thereafter. Estimated heart rate after 5 min of nose sling was significantly lower in HR gilts compared to LR gilts. Housing or backtest type did not affect heart rate variability indices. The results support the idea that the backtest relates to individual characteristics, which at an adult age also seem to play a role in the regulation of certain behavioral and physiological responses to short-term stress.

Animals↗

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

The stimulatory effect of vasopressin on the luteinizing hormone surge in ovariectomized, estradiol-treated rats is time-dependent.

The luteinizing hormone surge in the female rat is not only induced by the positive feedback of estradiol, but also by circadian signals originating in the suprachiasmatic nucleus (SCN). In a previous study we showed that administration of vasopressin, an SCN transmitter present in preoptic projections, induced an LH surge in animals bearing complete lesions of the SCN. This strongly suggests vasopressin as a stimulatory circadian signal for the timing of the LH surge. In the present study we investigated during which time window vasopressin may act in the medial preoptic area to stimulate LH secretion in SCN-intact female rats. Vasopressin or a specific V1a receptor antagonist was administered into the MPO by a reverse microdialysis technique during different time windows, and plasma LH concentrations were measured. Vasopressin stimulated the LH surge in 30% of the animals, when administered during the second half of the light period, but during the first half of the light period no effects were observed. Administration of the V1a receptor antagonist, however, did not affect the LH surge. These data confirm our previous results that vasopressin is a stimulatory factor for the LH surge also in SCN-intact animals, and indicate that a certain time window is available for such stimulation. We hypothesize that vasopressin in the SCN-intact animal may act as a circadian signal during a specific time window to induce the LH surge. The time window is the result of other SCN regulatory systems that are involved in the preparation of the LH surge.

Animals↗

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↗

PubMed2001

Regulation of cholecystokinin release from central nerve terminals.

The high abundance of the cholecystokinin octapeptide in various brain regions is expressed by involvement of this neuropeptide in diverse brain functions. This peptide is mostly, if not always, co-localized with classic transmitters in central nerve terminals. Since the functions of the coexisting transmitters are often different, differential regulation of their release is obvious. This differentiation is realized by differences in presynaptic localization, release dynamics, and calcium regulation. In addition, CCK release is locally modulated by receptors, kinases and phosphatases. The regulatory mechanisms of CCK release are placed into physiological perspective.

Animals↗

PubMed2001

CRH signalling in the bed nucleus of the stria terminalis is involved in stress-induced cardiac vagal activation in conscious rats.

The bed nucleus of the stria terminalis (BNST) is involved in autonomic and behavioral reactions to fearful stimuli and contains corticotropin-releasing hormone (CRH) fibers and terminals. The role of CRH in the medial part of the BNST in the regulation of heart rate (HR) and PQ interval of the electrocardiogram was studied under resting conditions and conditioned fear stress in freely moving rats. Microinfusion of CRH (0.2 microg/0.6 microl) in the medial BNST under resting conditions significantly enhanced HR as compared to saline treatment, but did not reduce the PQ interval, indicating that exogenous CRH in the medial BNST can activate both the sympathetic and parasympathetic cardiac outflow. In addition, CRH induced a slight increase in gross locomotor activity, an effect that succeeded the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but likely a direct effect of CRH. CF was induced by 10-min forced exposure to a cage in which the rat had experienced footshocks (5 x 0.5 mA x 3s) the day before. alpha-helical CRH(9-41) (alphahCRH; 5 microg/0.6 microl), a non-selective CRH receptor antagonist, or saline was infused into the medial BNST of rats prior to CF. CF induced freezing behavior, associated with an increase in HR and PQ interval, indicating activation of sympathetic and vagal outflow to the heart. alphahCRH significantly reduced the PQ response, but enhanced the tachycardia, suggesting inhibition of vagal activity. In addition, alpha-helical CRH(9-41) reduced the freezing response. Taken together, the data provide first evidence that CRH, released in the medial BNST during stress, contributes to cardiac stress responses, particularly by activating vagal outflow.

Animals↗

PubMed2001

Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression.

Earlier work has shown that plasma vasopressin levels of depressed patients were higher than those of healthy controls. The aim of the present study was to determine whether plasma vasopressin levels were correlated to parameters of the circadian rhythm. Forty-one patients with major depression and twenty-five controls participated in a case-control design under natural circumstances in a field study to investigate plasma vasopressin levels three times daily, circadian motor activity, and the 24-h periodicity of body temperature for five consecutive 24-h periods. Temperature measurements consisted of at least five, but mostly six or more measurements every 24 h. Twenty-two percent of the patients, but none of the controls lacked 24-h periodicity of body temperature. In melancholic patients increased vasopressin levels in plasma correlated with a weak 24-h periodicity of body temperature. The role of vasopressin is discussed in the light of the present findings.

Adult↗

PubMed2001

Control of the estradiol-induced prolactin surge by the suprachiasmatic nucleus.

In the present study we investigated how the suprachiasmatic nucleus (SCN) controls the E(2)-induced PRL surge in female rats. First, the role of vasopressin (VP), a SCN transmitter present in medial preoptic area (MPO) projections and rhythmically released by SCN neurons, as a circadian signal for the E(2)-induced PRL surge was investigated. Using a reverse microdialysis technique, VP was administered in the MPO during the PRL surge, resulting in a suppression of the surge. VP administration before the surge did not affect PRL secretion. Also, administration of a V1a receptor antagonist before the surge was ineffective. Second, lesions of the SCN were made that resulted in constant basal PRL levels, suggesting that with removal of the SCN a stimulatory factor for PRL secretion disappeared. Indeed, the PRL secretory response to blockade of pituitary dopamine receptors was significantly reduced in SCN-lesioned animals. These data suggest that the afternoon decrease of VP release in the MPO by SCN terminals enables the PRL surge to occur, and may thus be a circadian signal for the PRL surge. Simultaneously the SCN is involved in the regulation of the secretory capacity of the pituitary, possibly via specific PRL-releasing factors.

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

Responses to apomorphine of pigs with different coping characteristics.

RATIONALE: Classification of pigs based on the degree of resistance they display in a so-called "backtest" seems, to a certain extent, predictive for their coping strategy. OBJECTIVE: The present study examined whether, as found in rodents, the behavioral response to apomorphine of pigs relates to individual coping characteristics. METHODS: During the suckling period pigs were subjected to the backtest. In this test, each pig is restrained on its back for 1 min and the resistance (i.e. number of escape attempts) is scored. Pigs classified as low-resisting (LR, n=10) or high-resisting (HR, n=10) were selected. At 17-18 weeks of age they received a saline and an apomorphine injection (0.2 mg/kg SC) on 2 consecutive days in a balanced design. Behavior was recorded until 120 min after injection. RESULTS: Apomorphine increased locomotion in all pigs and reduced standing, standing alert and defecating. In addition, apomorphine induced the occurrence of some peculiar activities, rarely seen in saline-treated pigs, which seemed to represent either a transition between different postures or a conflict between hind- and forelimb activities. Apomorphine-treated LR pigs performed significantly more of these activities than HR pigs. However, snout contact with the floor, an oral stereotypy, was significantly increased in apomorphine-treated HR pigs, but not in apomorphine-treated LR pigs. CONCLUSIONS: In conclusion, the response to apomorphine of pigs relates to their behavioral response, high-resisting (HR) versus low-resisting (LR), in the backtest. The contrasts in behavioral response to apomorphine suggest a difference in the dopaminergic system between HR and LR pigs.

Adaptation, Psychological↗

PubMed2000

Condition-dependent presence of beta-lipotropin-like peptide in human keratinocytes.

This study aimed to characterize the beta-endorphin-immunoreactive material (betaE-IR) detectable in normal human keratinocytes (NHK). The effects of different culturing conditions and UV-irradiation on production of betaE-IR by NHK were assessed by radioimmunoassay and HPLC. All culture systems contained low levels of betaE-IR that was increased in conditioned media after UV-irradiation under certain conditions. NHK grown in nutrient-poor medium contained highest levels of betaE-IR that exhibited beta-lipotropin-like properties after HPLC analysis. The other culturing conditions displayed no authentic betaE-related peptides. Our results indicate that under certain culturing conditions NHK can produce POMC peptides like beta-lipotropin, which can be induced by UV-radiation.

Cells, Cultured↗

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↗