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Biomedical subjects

A Kalsbeek

Publications and source records attributed to A Kalsbeek.

At least 55 records · Page 3Linked to original sources
PubMed1996

Decrease of endogenous vasopressin release necessary for expression of the circadian rise in plasma corticosterone: a reverse microdialysis study.

The mammalian suprachiasmatic nuclei (SCN) contain an endogenous pacemaker that generates daily rhythms in behavior and secretion of hormones. Previously we hypothesized that the SCN imposes its circadian rhythm on the rest of the brain through a rhythmic release of its transmitters in its target areas. In the present study we employed microdialysis-mediated intracerebral administration of vasopressin (VP) and its V(1) -antagonist to study the mechanisms underlying the circadian control of the release of the adrenal hormone corticosterone. Stress-free application of the VP V(1) -antagonist in the dorsomedial hypothalamus of freely moving, undisturbed animals during the middle of the light period (i.e. the trough of the corticosterone rhythm) caused an immediate increase of circulating plasma corticosterone levels. A similar administration of VP at the end of the light period completely prevented the diurnal rise in plasma corticosterone. These results indicate a pronounced inhibitory role for SCN-derived VP at the level of the dorsomedial hypothalamus with respect to the activity of the hypothalamo-pituitary-adrenal axis during the day period. Thus, the daily decline in VP release sets a specific time window for the occurrence of the daily corticosterone peak. On the other hand, during the dark period corticosterone levels are decreasing together with basal VP levels. Therefore, in addition to the inhibitory VP signal from the SCN, there is also the need for an excitatory SCN signal in order to accomplish the complete circadian profile of plasma corticosterone.

Animals↗
PubMed1996

GABA receptors in the region of the dorsomedial hypothalamus of rats are implicated in the control of melatonin and corticosterone release.

Recently, anatomical evidence was presented that the mammalian circadian clock located in the suprachiasmatic nuclei (SCN) may utilize GABA to transmit diurnal information to the dorsomedial hypothalamus (DMH). The present study provides further physiological evidence for the involvement of this GABAergic projection in the regulation of diurnal rhythms. Infusion of the GABA agonist muscimol in the region of the DMH completely blocked the daily increase of plasma melatonin during darkness and reduced sympathetic output in the pineal gland resulting in lower pineal melatonin production, as measured with transpineal microdialysis. Further experiments in SCN-lesioned animals indicated that the origin of this inhibitory input to the DMH is indeed the SCN. The results of this study imply that the SCN can influence the sympathetic outflow of the hypothalamus through its GABA-containing projection. Furthermore, the present results probably explain the previously reported strong inhibitory effect of benzodiazepines on plasma melatonin in both animals and humans.

Animals↗
PubMed1995

In vivo measurement of a diurnal variation in vasopressin release in the rat suprachiasmatic nucleus.

Diurnal changes in the intranuclear release of vasopressin (VP) and oxytocin (OT) in the suprachiasmatic (SCN), paraventricular (PVN) and supraoptic nuclei (SON) of the rat were studied by means of brain microdialysis. A significant diurnal variation in VP release in the SCN was detected, with the highest levels occurring during midday and a trough around midnight. OT release from the SCN was below detection limit. The release of neither of these neurohypophysial peptides showed diurnal variations within the PVN or SON.

Animals↗
PubMed1994

Specific destruction of the serotonergic afferents to the suprachiasmatic nuclei prevents triazolam-induced phase advances of hamster activity rhythms.

Administration of Triazolam (Tz)--a short acting benzodiazepine (BZ)--induces permanent phase-shifts in locomotor activity of golden hamsters (Mesocricetus auratus). However, the target area(s) as well as the mechanism involved in the Tz-induced changes are not known. Previous results indicated that raphe nuclei (RN) would appear to be a likely site for Tz-induced phase shifts. Therefore, we specifically destroyed the 5-HT fibers connecting the RN with the SCN--the site of the endogenous mammalian clock--by microinjections of the selective neurotoxin 5,7 dihydroxytryptamine (5,7-DHT) at the level of SCN. Infusion of 5,7-DHT resulted in long lasting damage of the ascending serotonergic projection from RN to the hypothalamus. Subsequently, the phase-shifting effect of Tz was investigated. Only complete or almost complete depletion of the 5-HT input to the SCN was accompanied with a pronounced reduction of the phase shift together with a significant reduction of wheel-running activity during the 6 h following Tz injection. Our present results support the view that the 5-HT innervation of the SCN represents an essential link in the phase-shifting action following peripheral Tz injections.

5,7-Dihydroxytryptamine↗
PubMed1994

An attempt to correlate brain areas containing melatonin-binding sites with rhythmic functions: a study in five hibernator species.

High affinity melatonin-binding sites have been described, by means of autoradiography with 2-125I-melatonin as the ligand, in more than 60 brain areas of about 20 mammalian species, with dramatic variations in the nature and number of labelled structures among the different species studied. As melatonin is involved in the synchronization of biological rhythms, we have tried to correlate the brain areas containing melatonin-binding sites with some rhythmic functions typical of given species. Therefore, we have studied the location of melatonin-binding sites in the complete brain of five long-day breeders with hibernation cycles, viz. one insectivore and four rodents. With the exception of the suprachiasmatic nuclei and the pars tuberalis of the pituitary, both of which contain binding sites in all five species, few reactive structures are common, even among species from the same family, e.g. the edible dormouse and the garden dormouse.

Animals↗
PubMed1994

Effects of illumination and enucleation on substance-P-immunoreactive structures in subcortical visual centers of golden hamster and Wistar rat.

The undecapeptide substance P is found in different entities of the visual system that control eye movement and synchronize endogenous rhythms with the light cycle (i.e., superior colliculus, suprachiasmatic nucleus, intergeniculate leaflet). Immunocytochemical methods were used to compare the reactivity to substance P in the brain of five groups of golden hamsters and two groups of Wistar rats: (1) untreated hamsters kept under 14L:10D and sacrificed at noon; (2) identically maintained animals sacrificed at midnight; (3) enucleated animals kept under control conditions; (4) hamsters kept under constant darkness; (5) hamsters kept under the same conditions as the controls, but intraventricularly injected with colchicine. The results obtained in golden hamsters of groups (1) and (3) were compared with findings in Wistar rats treated accordingly [groups (6) and (7)]. Substance P-immunoreactive perikarya were found in the suprachiasmatic nucleus and superior colliculus of hamsters and Wistar rats. Substance P-immunoreactive nerve fibers were abundant in the hypothalamic area ventral to the paraventricular nucleus, in the intergeniculate leaflet, in some thalamic nuclei, and in the superior colliculus. Immunoreactivity to substance P in the suprachiasmatic nucleus and intergeniculate leaflet did not vary among the experimental groups. However, a conspicuous decrease in reactivity to substance P was observed in the superficial layers of the superior colliculus of enucleated hamsters and rats, compared with all other groups. These results indicate that substance P immunoreactivity in the superior colliculus, but not that in the suprachiasmatic nucleus or intergeniculate leaflet, depends on the integrity of the retinal projection.

Animals↗
PubMed1993

Induction of arousal in hibernating European hamsters (Cricetus cricetus L.) by vasopressin infusion in the lateral septum.

Vasopressin immunostaining in the lateral septum of the European hamster (Cricetus cricetus L.) disappears in autumn, at the time of the first appearance of hypothermic periods characteristic to hibernation. Previous results have shown that chronic administration of vasopressin in the lateral septum during winter prevents the expression of hypothermic periods, suggesting a role for this peptide in hibernation. It is now observed that acute infusion of vasopressin, and in 50% of the cases, of a specific vasopressin V1 receptor agonist, during a hypothermic period results in an immediate termination of hypothermia. Infusion of oxytocin or a vasopressin V2 receptor agonist were without effect. The results indicate that the seasonal variation in central vasopressin activity, possibly through an interaction with V1 receptors, may play an important role in the expression of hibernation in the European hamster.

Animals↗
PubMed1993

Efferent projections of the suprachiasmatic nucleus in the golden hamster (Mesocricetus auratus).

The efferent projections of the suprachiasmatic nucleus (SCN) in the golden hamster have been examined by using the anterograde tracer Phaseolus vulgaris leucoagglutinin (Pha-L). SCN projections were further localized through a combination of restricted SCN-lesions and immunocytochemistry for three well-known peptidergic transmitters contained in SCN neurons, viz. vasopressin (VP), vasoactive intestinal peptide (VIP), and gastrin-releasing peptide (GRP). Thus, major terminal fields of SCN-derived VP were detected in the medial preoptic nucleus, the anterior part of the paraventricular nucleus of the thalamus (PVA), the medial parvicellular part of the paraventricular nucleus of the hypothalamus (PVN), and the medial part of the dorsomedial nucleus of the hypothalamus (DMH). VIP-containing projections from the SCN were discovered in the PVA, anterior and dorsal parvicellular divisions of the PVN, subparaventricular area, and medial DMH. Efferent fibers from the SCN containing GRP were restricted to the subparaventricular area, medial DMH, and supraoptic nucleus. In addition, Pha-L tracing indicated the existence of SCN projections which could not be ascribed to one of the presently investigated peptides. Furthermore, a pronounced innervation of the contralateral SCN was observed, of which the neurotransmitter remains to be established. The results of the present study indicate that the different neuronal populations in the SCN, as characterized by their transmitter content, also show a clear diversity in their preferential target areas.

Animals↗
PubMed1993

No triazolam-induced expression of Fos protein in raphe nuclei of the male Syrian hamster.

While the visual projections to the suprachiasmatic nuclei (SCN) play a role in mediating the effects of light on circadian rhythms, the functional significance of the serotonergic projection from the raphe nuclei (RN) to the SCN is uncertain. Because previous results indicated that RN would appear to be a likely site for triazolam (Tz)-induced phase shifts, we used the expression of Fos-protein as a marker of Tz-induced neuronal activation. Immunocytochemistry was used to visualize the presence of Fos-like protein. Tz-induced Fos-labeled nuclei were found in superior colliculi, Edinger-Westphal nuclei (EW) and dorsal tegmental nuclei (DTg), but not in the RN. The SCN showed only occasionally labeled nuclei in all experimental groups, whereas there was no Tz-induced Fos-immunoreactivity in the intergeniculate leaflet (IGL). The present data not necessarily exclude the implication of the RN in the phase shifting effect of Tz. The phase shift could still be accomplished using a different set of immediate early genes (IEG), or without an IEG response. Alternatively, as will be discussed, other pathways could mediate the phase shifting effect of Tz.

Animals↗
PubMed1993

Vasopressin and vasoactive intestinal peptide infused in the paraventricular nucleus of the hypothalamus elevate plasma melatonin levels.

The connection between the suprachiasmatic nucleus (SCN) and the paraventricular nucleus of the hypothalamus (PVN) forms an important component of the melatonin rhythm-generating system. However, the chemical identity of this projection is not known. To test the possible implication of the SCN peptides vasopressin (VP) and vasoactive intestinal peptide (VIP) in this projection, we performed microinfusions in the PVN during the first half of the dark period and subsequently monitored resulting plasma melatonin levels. Infusions for 7 hr of either VP or VIP, but not oxytocin, caused increased plasma melatonin levels in the middle of the dark period. These observations confirm the role of the PVN in the melatonin rhythm-generating pathway and indicate that both VP and VIP released at the level of the PVN, and probably derived from the SCN, are able to influence peripheral plasma melatonin levels.

Animals↗
PubMed1993

Suprachiasmatic nucleus lesion increases corticosterone secretion.

The diurnal rhythm of corticosteroid secretion is controlled by the suprachiasmatic nucleus (SCN). In rats, plasma corticosteroid levels rise just before the onset of the activity period during the dark phase. Our previous results indicated that vasopressin as a neurotransmitter from the SCN inhibited corticosteroid secretion in the area of the paraventricular/dorsomedial nucleus of the hypothalamus. We hypothesized that during the day the SCN may serve as an inhibitory system for corticosteroid secretion. To investigate this possibility, intact and SCN-lesioned animals were exposed to mild stress in the morning and evening and their plasma corticosteroid levels were monitored. The results indicate that SCN-lesioned animals have higher morning corticosteroid levels and respond both in the morning and evening with higher corticosteroid levels after stress than do intact control animals. We conclude, therefore, that these results indicate an inhibitory role of the SCN on corticosteroid secretion. The apparent discrepancy with the reported stimulatory role of the SCN on adrenocorticotropic hormone secretion is discussed.

Animals↗
PubMed1992

Neonatal lesions of the ventral tegmental area affect monoaminergic responses to stress in the medial prefrontal cortex and other dopamine projection areas in adulthood.

A mean decrease of dopamine (DA) to 20% and serotonin to 25-30% of control levels was found in the medial prefrontal cortex (mPFC) and amygdala/piriform cortex (A/PC) of adult rats with neonatal lesions of the ventral tegmental area (VTA). The metabolites were less decreased suggesting an increased activity of the remaining terminals. Moderate decreases to 30-75% were detected for DA and serotonin in the nucleus accumbens, olfactory tubercle and striatum. Footshock stress in control animals resulted in a strong increase (200% of control) in DA metabolites in mPFC and A/PC. The noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in A/PC was strongly increased to 240%. When stress was given to the neonatally VTA-lesioned animals these neurochemical responses were reduced compared to the nonlesioned rats. In the case of DA in the mPFC this was clearly due to a loss of stress response in the severe lesion group where DA is depleted to less than 20% of control. The stress-induced small increases in DA metabolism in tubercle, accumbens and striatum and serotonin metabolism in the striatum (20-40%) were entirely lost, while the MHPG increase in the A/PC was blunted. The present results suggest that moderate and severe lesions of DA and serotonin alter or prevent the normal activation of these transmitter systems and even of the noradrenergic system to stress.

Aging↗
PubMed1992

Sexual differences and seasonal variations in vasoactive intestinal peptide immunoreactivity in the suprachiasmatic nucleus of jerboa (Jaculus orientalis).

The sexual differences and the seasonal variation in the vasoactive intestinal peptide (VIP) content of the suprachiasmatic nucleus (SCN) of a desert rodent, the jerboa (Jaculus orientalis) were studied using immunocytochemical techniques. During the period of sexual activity (spring-early summer), the VIP immunoreactivity in the SCN was higher in females than in males. In the period of sexual quiescence (autumn), both males and females exhibited an even more intense VIP immunoreaction in the SCN as compared to spring. However, during this period, the sex-related differences in the VIP content of the SCN observed in spring were no longer detectable. The direct possible influence of sex hormones on the VIP content in the SCN, and the physiological significance of the seasonal variation observed in the VIP immunoreactivity in the SCN in this species remains to be determined.

Animals↗
PubMed1992

Vasopressin-containing neurons of the suprachiasmatic nuclei inhibit corticosterone release.

The suprachiasmatic nucleus (SCN) is the major pacemaker in the central nervous system responsible for generating circadian rhythmicity in mammals. Tracer studies show limited projections of the SCN, mainly to the paraventricular nucleus of the thalamus and paraventricular and dorsomedial nuclei of the hypothalamus, suggesting that the latter two areas may be the target areas of the SCN for controlling corticosterone release. The present results show that when infused in the paraventricular/dorsomedial nucleus of the hypothalamus femtomolar concentrations of vasopressin (VP), but not vasoactive intestinal peptide (VIP), are able to suppress elevated levels of corticosterone in SCN-lesioned animals to basal daytime values. On the other hand, infusion of the VP antagonist in the same hypothalamic area induced a sevenfold increase of basal corticosterone levels in intact animals. The SCN origin of this VP input was established in SCN-lesioned animals where no difference between the effect of infusing the antagonist or Ringer could be detected. These results imply that the SCN can influence the daily corticosterone rhythm through its VP-containing projection to the paraventricular/dorsomedial nucleus of the hypothalamus.

Animals↗
PubMed1989

Ontogeny of open field activity in rats after neonatal lesioning of the mesocortical dopaminergic projection.

In order to examine the effect of neonatal depletion of the dopaminergic mesocortical projection on the development of a prefrontal cortex-mediated behaviour the ontogeny of open field behaviour was studied after neonatal depletion of cortical dopamine. Cortical dopamine was depleted by neonatal thermal lesions of the ventral tegmental area (VTA). Medial VTA lesions caused a moderate dopamine depletion in the prefrontal cortex and an almost complete cortical serotonin depletion, and resulted in transient hyperactivity in the open field at postnatal day 25. More extensive VTA lesions produced an almost complete depletion of dopamine in the prefrontal cortex, but also affected the dopaminergic innervation of the nucleus accumbens, and resulted in a permanent hypoactivity in locomotor and exploratory behaviour in the open field. The effects of neonatal lesions of the mesolimbocortical projection are quite different from those made in adulthood. These results indicate in addition that, apart from the dopamine/noradrenaline balance, the serotonin/dopamine interactions in the frontal cortex may also be of importance in regulating open field activity.

Age Factors↗
PubMed1989

Monoamine and metabolite levels in the prefrontal cortex and the mesolimbic forebrain following neonatal lesions of the ventral tegmental area.

Monoamine metabolism was determined in the medial prefrontal cortex (mPFC) and the limbic forebrain (LFB) of adult rats following neonatal lesions of the ventral tegmental area. The dopamine (DA) and serotonin (5-HT) levels were decreased down to 30% in both the mPFC and the LFB. The noradrenaline (NA) level was also significantly decreased, but only in the mPFC of the right hemisphere. The metabolite/transmitter ratios of DA and 5-HT, but not of NA, were greatly increased in the depleted mPFC, but not in the LFB, which suggests an increased activity of the remaining cortical DA and 5-HT fibres in the mPFC.

Animals↗