Biomedical subjects

M Fluttert

Publications and source records attributed to M Fluttert.

8 recordsLinked to original sources

PubMed2001

Cardiovascular and behavioural responses to psychological stress in spontaneously hypertensive rats: effect of treatment with DSP-4.

We used a model of psychological stress combining exposure to an open-field novel environment, radio-telemetric measurement of blood pressure and heart rate, and behavioural tracking analysis of behavioural parameters. All rats showed significant increases in blood pressure and heart rate for the duration of open-field exposure, with spontaneously hypertensive rats (SHR) showing markedly greater pressor responses and tachycardia when compared to either Wistar-Kyoto (WKY) or Sprague-Dawley rats (SD rats). Behavioural responses in the open-field were unrelated to the magnitude of cardiovascular responses. Open-field exposure on 4 consecutive days induced similar pressor responses and tachycardia on each day. By contrast, behavioural responses were reduced from the second day of open-field exposure. Treatment of SHR and WKY rats with DSP-4, to deplete central noradrenaline levels, did not affect cardiovascular responses in SHR, whereas WKY rats showed a trend towards inhibition. However, in WKY rats, but not SHR, DSP-4 treatment caused a marked reduction in behavioural activity in the open-field. In conclusion, these data show that: (1) SHR display marked cardiovascular hyperreactivity to psychological open-field stress when compared to two normotensive rat strains; (2) unlike behavioural responses, cardiovascular stress responses do not habituate upon repeated stress exposure; and (3) noradrenergic projections from the locus coeruleus do not appear to play a major role in cardiovascular stress responses in SHR or WKY rats, although they may be involved in behavioural responses in WKY rats.

Adrenergic Agents↗

PubMed2001

Blood pressure, heart rate, and behavioral responses to psychological "novelty" stress in freely moving rats.

We developed a new model of psychological "open-field" stress in freely moving rats. Blood pressure and heart rate of the rats were measured by radiotelemetry and behavior analyzed by video tracking software. Open-field exposure induced marked increases in blood pressure and heart rate. Repeated daily exposure induced pressor responses that were slightly higher on Day 4 when compared to Day 1. Pretreatment with the beta1-adrenoceptor antagonist atenolol inhibited the tachycardia whereas the ganglion blocker pentolinium inhibited the pressor response, indicating involvement of the sympathetic nervous system. Pretreatment with diazepam prevented the novelty stress-induced pressor response and reduced the tachycardia. These results show that the psychological stress of exposing rats to an open field induces marked cardiovascular effects that are mediated by sympathetic hyperactivity. This model is unique in that it focuses on psychological stress and allows concomitant measurement of blood pressure, heart rate, and behavior in freely moving rats.

Animals↗

PubMed2001

Differential and age-dependent effects of maternal deprivation on the hypothalamic-pituitary-adrenal axis of brown norway rats from youth to senescence.

In this study, the hypothesis was tested that infants deprived from maternal care show persistent changes in hypothalamic-pituitary-adrenal activity. For this purpose, we studied the effect of maternal deprivation in one cohort of the healthy ageing Brown Norway rat strain showing still more than 80% survival rate at 32 months of age. Three-day-old male Brown Norway rats were either maternally deprived for 24 h or remained with the dam. In 3, 12 and 30-32 months (young, adult, senescent) deprived rats and their nondeprived littermates (controls), we determined basal resting and stress-induced plasma adrenocorticotropic hormone (ACTH) and corticosterone as well as corticotropin releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus. Mineralocorticoid (MR) and glucocorticoid receptors (GR) in hippocampus and PVN were also assessed using in vitro cytosol binding and in situ hybridization. The effect of ageing per se showed that in the control nondeprived Brown Norway rats, basal corticosterone and ACTH concentrations did not change during life. However, with age, the corticosterone response to novelty stress became progressively attenuated, but prolonged, while there was an age-related increase in the ACTH response. CRH mRNA expression in PVN decreased with age. Hippocampal MR binding and MR mRNA expression in the dentate gyrus were reduced at senescence, as were the GR binding capacities in hippocampus and hypothalamus. Maternal deprivation did not affect survival rate, body weight, nor adrenal weight of the ageing Brown Norway rats. Basal corticosterone and ACTH levels were not affected by deprivation, except for a rise in basal corticosterone concentrations at 3 months. At this age, the corticosterone output in response to novelty was attenuated in the deprived rats. In contrast, a striking surge in novelty stress-induced corticosterone output occurred at midlife while, at senescence, the corticosterone and ACTH responses were attenuated again in the deprived animals, particularly after the more severe restraint stressor. CRH mRNA expression was reduced only during adulthood in the deprived animals. After maternal deprivation, the MR mRNA in dentate gyrus showed a transient midlife rise. GR binding in hypothalamus and hippocampus GR binding was reduced in young rats while, in the senescent deprived animals, a reduced GRmRNA expression was observed in PVN and hippocampal CA1. In conclusion, in the Brown Norway rat, ageing causes a progressive decline in corticosterone output after stress, which is paralleled at senescence by decreased MR and GR mRNA expression in hippocampus and hypothalamus. The long-term effects of maternal deprivation become manifest differently at different ages and depend on test conditions. The deprivation effect culminates in a midlife corticosterone surge and results at senescence in a strongly reduced corticosterone output.

Adrenocorticotropic Hormone↗

PubMed2000

Maternal deprivation affects behaviour from youth to senescence: amplification of individual differences in spatial learning and memory in senescent Brown Norway rats.

Previous studies have shown that deprivation of the infant rat from maternal care has pronounced effects on the stress system during ontogeny. Here we test the hypothesis that 24 h of maternal deprivation at postnatal day 3 will cause persistent changes in behaviour. Spatial learning and memory of male Brown Norway rats deprived as infants were observed in the Morris water maze at 3, 12, 24 and 30-32 months of age (young, adult, aged, senescent). Their nondeprived mother-reared littermates served as controls. (i) With increasing age, water maze performance declined in deprived and nondeprived groups. However, once the task was learned the animals maintained their good performance during retest at later ages. (ii) Maternal deprivation delayed acquisition until adulthood and caused at every age a higher degree of persistent behaviour as judged from the performance of deprived rats' free swim trials and reversal trials. (iii) At senescence the mean performance in the water maze did not differ between the groups. Instead, the individual performance was strikingly different within each group. Senescent deprived rats were either nonimpaired or impaired with only a few animals showing an intermediate performance. Thus, a large group of animals ( approximately 40%) ages successfully as they are resistant to the effect of maternal deprivation. In contrast, the majority of the control animals displayed intermediate performance. Taken together, maternal deprivation has life-long consequences for behaviour and culminates at senescence in amplification of individual differences in learning ability rather than in a generalized deterioration of cognitive functions.

Aging↗

PubMed2000

A refined method for sequential blood sampling by tail incision in rats.

Levels of endogenous or administered substances can be estimated by blood sampling. This allows an evaluation of the relationship between clinical signs, physiological parameters, pharmacological treatments and behaviour of the animal. We show that blood samples can be taken occasionally as well as sequentially by means of a small incision at the end of the rats' tails. Up to 300 microl of blood can be collected within 90 s. The advantages of this method are: (i) anaesthesia and surgery or restraint of the animal are not necessary; (ii) the procedure can be considered stress-free as indicated by the low, basal levels of the stress hormone corticosterone, even with frequent sequential blood sampling over 3 h; and (iii) it can be used for longitudinal studies allowing intra-individual comparisons over months and even years. Blood samples collected via an intravenous catheter and, at the same time, by our tail incision method resulted in comparable amounts of corticosterone. Moreover, we consider the tail incision method for rats to be 'animal-friendly' and a real alternative to other conventionally used blood sampling techniques.

Animals↗

PubMed1998

Acute blockade of hippocampal glucocorticoid receptors facilitates spatial learning in rats.

Corticosteroids can facilitate or impair learning and memory processes. We found that the glucocorticoid receptor antagonist RU38486 injected locally into the dorsal hippocampus dose-dependently improved the performance of male Wistar rats in the water maze 24 h after treatment. This observation suggests a discrete specificity of hippocampal glucocorticoid receptors in facilitation of memory.

Animals↗

PubMed1998

Continuous blockade of brain glucocorticoid receptors facilitates spatial learning and memory in rats.

Previously, a corticosterone surge associated with a learning task was shown to facilitate cognitive processes through brain glucocorticoid receptors (GR) while chronic overexposure to this stress hormone impaired cognition. In the present study we tested the hypothesis that opposing effects on learning and memory might also occur after either phasic or continuous blockade of brain GR by intracerebroventricular (i.c.v.) administration of the GR antagonist RU38486 (aGR). We used a Morris water maze procedure to assess spatial learning and memory abilities in male Wistar rats. The effect of phasic brain GR blockade was studied following daily pretraining administration of 10 and 100 ng/microL aGR i.c.v. on 3 consecutive days. This repetitive aGR treatment impaired spatial learning and memory dose-dependently in comparison with vehicle controls. For continuous brain GR blockade, animals received an i.c.v., infusion of aGR (10 and 100 ng/0.5 microL per h or vehicle) over 10 days. Infusion of 100 ng aGR per hour resulted in a long-lasting facilitation of spatial performance. The 10 ng aGR infusion also caused initially a facilitating effect, which was, however, transient and performance became impaired during retest. Possible anxiolytic properties of the drugs were excluded in view of the animals' behaviour in the elevated plus maze. Both doses of aGR infusion reduced the number of mineralocorticoid receptors in the hippocampus, but only the high dose of aGR resulted in a significant reduction of available GR sites. In conclusion, continuous administration of GR antagonist improves cognitive function, while phasic blockade of brain GR function causes a cognitive deficit.

Adrenocorticotropic Hormone↗

PubMed1994

The effect of corticosterone on reactivity to spatial novelty is mediated by central mineralocorticosteroid receptors.

Corticosterone, secreted by the adrenal glands, binds to central mineralocorticoid receptors with high affinity and to glucocorticoid receptors with a tenfold lower affinity. In previous studies we have shown that the selective activation of either mineralocorticoid receptors or glucocorticoid receptors exerts distinctly different behavioural effects. In this study we examined in particular the mineralocorticoid receptor-mediated effect of corticosterone on the control of the behavioural response of male Wistar rats to spatial novelty. This analysis was based on our observation that in adrenal-intact rats the presence of an object in the centre of an open field alters the time spent and distance walked in the centre compared to the peripheral area, i.e. the pattern of reactive locomotor activity is changed. Using this paradigm we found that 1 day after removal of the adrenals the rats increased their behavioural reactivity towards the object. Treatment of adrenalectomized rats with a low dose of corticosterone (50 micrograms/kg s.c.) 1 h prior to testing restored the behavioural reactivity to the level of sham-operated, intact rats. Surprisingly, a high dose of corticosterone (1000 micrograms/kg s.c.) also increased the rat's reactivity towards the object. The same high dose of corticosterone given to adrenal-intact rats also increased behavioural reactivity. Pretreatment of these rats with an intracerebroventricular injection of the selective mineralocorticoid receptor antagonist RU28318 (100 ng/microliters) prevented the corticosterone-induced increase in behavioural reactivity, while the blockade of glucocorticoid receptors with the antagonist RU38486 (100 ng/microliters) was not effective. Administration of the mineralocorticoid receptor antagonist without corticosterone to adrenal-intact rats also increased behavioural reactivity, but this increase did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗