Biomedical subjects

D H Versteeg

Publications and source records attributed to D H Versteeg.

At least 73 records · Page 4Linked to original sources

PubMed1985

Behavioural factors contribute to the development of spontaneous hypertension in rats.

The relationship was studied between brain catecholamine systems, open-field behaviour and the development of hypertension in spontaneously hypertensive rats (SHR). Both the rise in blood pressure and the increased open-field rearing activity of SHR were inhibited by central dopamine depletion. Antihypertensive treatment with hydralazine or captopril did not change behaviour, however. It is suggested that central dopamine systems may form a link between changes in behaviour of SHR and the development of hypertension in this strain. The changes in behaviour may underlie rather than be the result of the hypertension.

Animals↗

PubMed1984

Pro-Leu-GlyNH2 affects dopamine and noradrenaline utilization in rat limbic-forebrain nuclei.

The effects of Pro-Leu-GlyNH2 (PLG), administered i.c.v. in doses of 3.5, 35, 350 and 3500 pmol, were studied on the alpha-MPT-induced disappearance of catecholamines in microdissected rat brain nuclei. PLG, dose-dependently, increased dopamine disappearance in the nucleus caudatus and globus pallidus, whereas a decrease in dopamine disappearance was observed in the nucleus dorsomedialis. Noradrenaline disappearance was decreased in the medial septal nucleus, anterior hypothalamic area and lateral amygdala. A tendency towards an increase in noradrenaline disappearance was observed in the nucl. supraopticus. These data show that PLG has a central site of action. The effects of PLG on dopamine disappearance are comparable to those previously found with vasopressin, while the effects of PLG on noradrenaline utilization show a striking similarity with those previously obtained with oxytocin.

Animals↗

PubMed1984

Regional brain catecholamine levels and the development of hypertension in the spontaneously hypertensive rat: the effect of 6-hydroxydopamine.

To investigate the role of central catecholaminergic pathways in the development of hypertension in the spontaneously hypertensive rat (SHR) the effects of intracerebroventricular (i.c.v.) injections of 6-hydroxydopamine (6-OHDA) were compared with those of local injections near the main ascending noradrenergic pathways. The parameters studied were systolic blood pressure, heart rate and regional catecholamine concentrations in micropunched brain areas. I.c.v. treatment with 6-OHDA (three 200 micrograms injections) of young SHR attenuated the development of hypertension and caused widespread depletion of noradrenaline and to a lesser extent of dopamine and adrenaline. 6-OHDA-induced lesions of the dorsal and ventral noradrenergic bundles did not affect the rise in blood pressure but induced a depletion of forebrain noradrenaline comparable to that after the i.c.v. treatment. Dopamine and adrenaline levels were, however, not substantially affected. These results suggest that forebrain noradrenergic innervation may not be of major importance for the development of hypertension in the SHR.

Animals↗

PubMed1984

Pre-decapitation state of arousal of rats predetermines the effect of des-Tyr1-gamma-endorphin on dopamine release from nucleus accumbens slices in vitro.

The non-opiate beta-endorphin fragment des-Tyr1-gamma-endorphin (DT gamma E) had a decreasing effect on K+-induced release of tritiated dopamine from nucleus accumbens slices in vitro, when tissue was used of rats which prior to decapitation were in a state of low arousal. When nucleus accumbens tissue was used of rats which were mildly stressed by exposure to a novel environment prior to decapitation, this effect was absent, while an enhancing effect of DT gamma E became evident on basal dopamine efflux. This latter effect resembled that of haloperidol, which dose-dependently enhanced basal dopamine efflux in vitro. Exposure of rats to ether vapor shortly before decapitation abolished both these in vitro effects of DT gamma E. The results are interpreted as indicating that the quality of the modulating effects of DT gamma E on dopamine release from dopaminergic neurons projecting to the nucleus accumbens is depending on the state of activity of these neurons, which, in its turn, is a reflection of the state of arousal of the rats.

Animals↗

PubMed1984

Microinjection of vasopressin and two related peptides into the amygdala: enhancing effect on local dopamine neurotransmission.

The effects of local microinjection of Arg8-vasopressin, cyclo[Lys-Gly] and L-Pro-L-Leu-GlyNH2 (PLG) were studied on the alpha-MPT-induced disappearance of dopamine and noradrenaline in the amygdala and in a number of other brain regions. A dose-dependent increase in dopamine utilization was found in the amygdala after local microinjection of Arg8-vasopressin, cyclo[Lys-Gly] and PLG at doses of 0.1, 2.7 and 18 pmol respectively. No effects were found on noradrenaline utilization in this brain region. Using a microdissection method, it was found that cyclo[Lys-Gly] enhanced dopamine utilization in the nucl. amygdaloideus centralis, whereas the effect of PLG was mainly located in the nucl. amygdaloideus corticalis. These effects of Arg8-vasopressin, cyclo[Lys-Gly] and PLG on dopamine utilization in the amygdala are correlated with those on avoidance behavior and can be interpreted as in support of the role of dopamine as neurotransmitter involved in retrieval processes.

Amygdala↗

PubMed1984

Acute changes in dopamine metabolism in the medio-basal hypothalamus following adrenalectomy.

During the first hour following adrenalectomy the alpha-MPT-induced disappearance of dopamine was increased in the arcuate nucleus compared to that in sham-operated rats. In a number of other brain regions of both adrenalectomized and sham-adrenalectomized rats only stress-induced changes were observed in catecholamine utilization. These data suggest that corticosterone selectively modulates dopamine utilization in the medio-basal hypothalamus.

Adrenalectomy↗

PubMed1984

Oxytocin affects utilization of noradrenaline in distinct limbic-forebrain regions of the rat brain.

The effects of oxytocin, administered intracerebroventricularly in doses of 1, 10, 100 and 1000 pmol, were studied on the disappearance of catecholamines induced by alpha-methyl-p-tyrosine in microdissected nuclei of the rat brain. Oxytocin dose-dependently decreased the utilization of noradrenaline in the lateral and medial septal nuclei and anterior hypothalamic area, whereas an enhanced utilization was observed in the nucleus supraopticus. Tendency towards a change in utilization of noradrenaline was found in the dorsal septal nucleus and the lateral amygdala. Utilization of dopamine was not significantly affected in any of the nuclei of the brain studied. Tendency towards a decrease in utilization of dopamine was observed in the nucleus caudatus, globus pallidus and medial septal nucleus. It thus appears that oxytocin elicited changes in only a restricted number of brain nuclei. Interestingly, these nuclei contain cell bodies (nucleus supraopticus) and terminals (other nuclei) of the oxytocin system in the brain. Though the effects of oxytocin were not as widespread as those previously seen after administration of vasopressin, it is worthy of note that, in general, the effects of oxytocin were opposite to those seen after vasopressin. The opposite effects of vasopressin and oxytocin on catecholamine metabolism could be related to the opposite effects of the two peptides on behaviour, neuroendocrine and autonomic regulation.

Animals↗

PubMed1984

Depressor activity of intracerebroventricularly administered pepstatin in young spontaneously hypertensive rats.

The effect of prolonged intracerebroventricular (i.c.v.) infusion of N-acetyl-pepstatin in young and adult spontaneously hypertensive rats was studied. In young animals, pepstatin infusion resulted in a decrease in blood pressure and heart rate. Water intake and body weight were not affected. The depressor effect was accompanied by a slight increase in plasma renin activity and decreases in plasma vasopressin and plasma catecholamines. The blood pressure of adult rats with already established hypertension was not significantly affected. In addition, changes in plasma renin or catecholamines were not observed in these animals while vasopressin levels were slightly increased. The involvement of a possibly decreased sympathetic activity in the depressor effect of pepstatin is suggested. It is concluded that increased brain renin activity contributes to the development of hypertension of spontaneously hypertensive rats.

Aging↗

PubMed1983

Electrical stimulation of the ventral tegmental area and catecholamine metabolism in discrete regions of the rat brain.

Data are presented which show a different pattern of dopamine and noradrenaline utilization in terminal regions of the A9 and A10 dopaminergic systems and in terminal regions of the dorsal noradrenergic bundle after electrical stimulation of the ventral tegmental area and an adjacent area. At the sites of the electrodes an enhanced turnover of noradrenaline was found. These results are discussed relating the location of the electrode sites and the location of the dopaminergic cell bodies A9 and A10 and catecholaminergic fibers passing through the MFB innervating forebrain and limbic structures. It is concluded that activation of parts of the A10 dopaminergic system and the A6 noradrenergic system is correlated with intracranial self-stimulation.

Animals↗

PubMed1983

The identification of specific serotonergic nuclei inhibited by cardiac vagal afferents during acute myocardial ischemia in the rat.

Cardio-cardiac autonomic reflexes mediated by the cardiac vagus during acute myocardial infarction play an important role in determining post-infarction hemodynamic function and the susceptibility of the infarcting heart to lethal arrythmias. In an earlier study we had demonstrated that serotonin-containing neurons in the brain participate in the mediation of these reflexes following left coronary artery ligation in the rat. In this study we identify brain serotonin nuclei involved. The accumulation of serotonin was measured in 19 brain nuclei from rats treated with pargyline, a monoamine oxidase inhibitor. The rats were subjected to either left coronary artery ligation or sham operation with or without bilateral cervical vagotomy or lidocaine applied topically only to the left ventricle. Serotonin accumulation was markedly reduced in the nucleus hypothalamicus posterior, nucleus raphe magnus and nuclei-raphe medianus-centralis superior in the rats subjected to coronary artery ligation as opposed to sham operation; no other brain regions were affected. The topical application of lidocaine to the left ventricle or vagotomy completely obviated the ligation-induced decrease in serotonin turnover. We conclude that there is an inhibition of serotonergic activity in the nucleus hypothalamicus posterior, nucleus raphe magnus and nuclei raphe medianus-centralis superior following left ventricular myocardial infarction in the rat. The afferent signal arises from receptors in the left ventricle and is conducted by the vagus.

Animals↗

PubMed1983

Aldosterone blocks the response to corticosterone in the raphe-hippocampal serotonin system.

The accumulation of serotonin induced by the monoamino oxidase inhibitor pargyline was used as an index for 5-HT turnover in the dorsal hippocampus and raphe area. A low dose of corticosterone administered s.c. immediately after adrenalectomy significantly increased serotonin turnover in both regions over the subsequent 1 h interval. The same dose of aldosterone was ineffective, but pretreatment with aldosterone blocked the serotonin response to corticosterone in the acutely adrenalectomized rat. [3H]Corticosterone administered to adrenalectomized rats was not retained by cell nuclei of the raphe area in a limited capacity manner as occurred in the hippocampus. Pretreatment with aldosterone blocked the uptake of [3H]corticosterone in hippocampal cell nuclei. It is concluded that corticosterone triggers a serotonin response and that the specificity of the corticosterone action suggests involvement of the steroid receptor system located postsynaptically to the raphe-hippocampal serotonin projection.

Aldosterone↗

PubMed1983

Sites of behavioral and neurochemical action of ACTH-like peptides and neurohypophyseal hormones.

In order to localize the site of action of neuropeptides in relation to their effects on behavior and memory various approaches have been used. As a result of studies using rats bearing lesions in different areas of the limbic system as well as of studies in which neuropeptides were locally applied into various areas of the brain it appeared that the limbic system (amygdala, hippocampus, septum and some thalamic areas) plays an essential role in the effect of vasopressin and ACTH and their derivatives on behavior and memory. Neurochemical studies generally indicate that changes occur in catecholamine utilization in these various limbic regions upon administration of these neuropeptides. It can be concluded that the effects of vasopressin in the terminal regions of the coeruleo-telencephalic noradrenalin system correlate with its effects on consolidation of memory. It is likely that the effects of vasopressin on other transmitter systems (e.g. dopamine in the amygdala and serotonin in the hippocampus) correspond with the effect of this neuropeptide on retrieval processes. In addition, regional differences in biotransformation of the neurohypophyseal hormones suggest that different patterns of behaviorally active fragments of these peptides may be present locally in the brain.

Adrenocorticotropic Hormone↗

PubMed1983

Inhibitory avoidance deficit following short-term adrenalectomy in the rat: the role of adrenal catecholamines.

Impaired retention of an inhibitory avoidance response was observed in rats subjected to adrenalectomy (ADX) up to 120 hr before the single learning trial. Corticosterone substitution failed to normalize this behavioral deficit. Rats ADX 240 hr prior to the learning trial showed a normalized behavior. Adrenomedullectomy (ADXM) 48 or 240 hr before learning caused a similar impairment as in short-term ADX rats. The 240-hr ADX rats subjected to corticosterone substitution showed the same behavioral deficit as short-term ADX rats or ADXM ones. Immediate postlearning subcutaneous injection of adrenaline in a dose range of 0.005-5.0 micrograms/kg or of noradrenaline (0.005-0.5 microgram/kg) to 48-hr ADX rats resulted in a dose-related improvement of later retention behavior. Higher doses of catecholamines were less or ineffective. Postlearning treatment of 48-hr ADXM rats with adrenaline (0.5-500 micrograms/kg) caused a similar pattern of behavioral changes. It is concluded that adrenal catecholamines play an important role in the modulation of consolidation of memory. In addition, the high circulating ACTH levels that follow long-term ADX may correct for the behaviorial deficit induced by the absence of adrenomedullary catecholamines.

Adrenal Glands↗

PubMed1982

Effect of N,N-dimethyl-p-methoxyphenylethylamine on blood pressure and brain catecholamines in DOCA-saline hypertensive rats.

Intraperitoneal and intraventricular injections of N,N-dimethyl-p-methoxyphenyl ethylamine (PMPEA) decreased blood pressure in conscious DOCA-saline hypertensive rats. Bilateral injection of this agent into the nucleus tractus solitarii (NTS) of anaesthetized normotensive rats also caused a decrease in blood pressure. The increased turnover of noradrenaline in the dorsal part of the caudal medulla oblongata in DOCA-saline hypertensive rats was found to be restored to normal following treatment with N,N-dimethyl PMPEA. The data indicate a central site of action for the antihypertensive effect of N,N-dimethyl PMPEA.

Animals↗

PubMed1982

The effects of des-enkephalin-gamma-endorphin and des-Tyr1-a-endorphin on regional serotonin metabolism in rat brain.

Des-enkephalin-gamma-endorphin (beta-endorphin6-17; DE gamma E) causes a significant reduction of the serotonin concentration of the raphe area of the mesencephalon and of the dorsal hippocampus of the rat. DE gamma E does not, however, alter the pargyline-induced accumulation of serotonin in either of these two brain regions or in the mediobasal hypothalamus. Des-Tyr1-a-endorphin (beta-endorphin2-16; DTaE), on the other hand, inhibits the accumulation of serotonin following MAO-inhibition by pargyline in all 3 brain regions, while, in addition to causing a transient reduction in the serotonin concentration of the raphe area, it decreases the serotonin concentration of the mediobasal hypothalamus. These results indicate that DE gamma E and DTaE, which have been shown to exert opposite effects on behavior in various behavioral tests, both affect regional serotonin metabolism in rat brain and that they do so differently.

Animals↗

PubMed1982

Effect of des-Tyr1-gamma-endorphin on serotonin metabolism in rat brain regions.

Intracerebroventricular (i.c.v.) administration of des-Tyr1-gamma-endorphin (0.1 and 1.0 microgram) caused a decrease of the serotonin (5-HT) concentration of the hippocampus. The concentration of 5-HIAA and the pargyline-induced alterations in 5-HT and 5-HIAA were not affected. No effects were noticed in other brain regions.

Animals↗

PubMed1982

Decreased serotonin turnover in the dorsal hippocampus of rat brain shortly after adrenalectomy: selective normalization after corticosterone substitution.

Pargyline-induced accumulation of serotonin (5-HT) was used as an index of 5-HT turnover rate in the dorsal hippocampus. One hour after bilateral removal of the adrenals, 5-HT turnover was significantly reduced when compared to that of the sham-operated controls. A low dose of corticosterone given immediately after adrenalectomy restored the 5-HT response, while the same dose of dexamethasone was ineffective. Pretreatment with dexamethasone blocked the 5-HT response to corticosterone in the acutely adrenalectomized rat. The specificity of the 5-HT response in the hippocampus corresponds to the properties of the glucocorticoid receptor system in rat hippocampal neurons.

Adrenal Glands↗

PubMed1982

The identification of specific brain nuclei in which catecholamine turnover is increased by left ventricular receptors during acute myocardial infarction in the rat.

Central catecholaminergic nerves have been shown to participate in the integration of cardio-cardiac reflexes induced by coronary artery ligation in the rat. In this study we measured the turnover of dopamine, norepinephrine and epinephrine in microdissected brain regions to identify some of the specific neural loci involved in this integration. Three groups of rats, treated with alpha-methyltyrosine, an inhibitor of catecholamine biosynthesis were examined: left coronary artery ligation, left coronary artery ligation with the left ventricle painted with lidocaine, and sham operation. An untreated group of resting rats was also examined. Dopamine, norepinephrine and epinephrine turnover was increased in ligated rats in nucleus tractus solitarius (right and left), nucleus commissuralis, A1-region, locus coeruleus, nucleus cuneatus, and area postrema in the pons-medulla and nucleus dorsomedialis in the hypothalamus. Norepinephrine and dopamine (but not epinephrine) turnover was increased in nucleus ambiguus in the brain stem and nucleus paraventricularis in the hypothalamus. A ligation-induced increase in norepinephrine turnover, alone, was exhibited by the A2-region and nucleus gigantocellularis in the medulla and nucleus supraopticus and nucleus hypothalamicus posterior in the hypothalamus. Dopaminergic nerves to the nucleus gigantocellularis appeared to be inhibited following coronary ligation. The catecholamine stores of 11 nuclear regions were not influenced by coronary artery occlusion. Topical lidocaine, applied to the ischemic left ventricle, only, of ligated rats, completely restored regional brain catecholamine turnover to that found in sham-operated animals. In conclusion, we have identified discrete loci in the brain in which catecholamine turnover (as measured by alpha-methyltyrosine induced disappearance) is increased by the stimulation of left ventricular receptors during acute myocardial ischemia in the rat.

Animals↗