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Biomedical subjects

G Telegdy

Publications and source records attributed to G Telegdy.

At least 199 records · Page 11Linked to original sources

Effects of oxytocin, des-glycinamide-oxytocin and anti-oxytocin serum on the alpha-MPT-induced disappearance of catecholamines in the rat brain.

Oxytocin (OXT) attenuates memory processes and endogenous OXT might be regarded as an amnesic neuropeptide. In this study, the mode of action of OXT on brain catecholaminergic neurotransmission has been analyzed. Peripheral injection of OXT facilitated the alpha-MPT-induced disappearance of noradrenaline (NA) in the mesencephalon. Dopamine (DA) disappearance was inhibited in the mesencephalon and facilitated in the striatum. The accelerated striatal DA disappearance was not observed if the peptide was given together with alpha-MPT, but only if OXT was injected after alpha-MPT treatment. Intraventricular injection of OXT or des-glycinamide-oxytocin (DG-OXT) caused a decrease in the DA disappearance in the mesencephalon, whereas central administration of anti-oxytocin serum (anti-OXT) accelerated the DA disappearance in the same region. The data raise the possibility that DA utilization in the mesencephalon may be correlated with the influence of OXT on CNS processes.

Animals↗

Structure-activity and dose-effect relationships of the antagonism of picrotoxin-induced seizures by cholecystokinin, fragments and analogues of cholecystokinin in mice.

Intraperitoneal administration of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and nonsulphated cholecystokinin octapeptide (CCK-8-NS) enhanced the latency of seizures induced by picrotoxin in mice. Experiments with N- and C-terminal fragments revealed that the C-terminal tetrapeptide (CCK-5-8) was the active centre of the CCK octapeptide molecule. The analogues CCK-8-SE and CCK-8-NS (dose range 0.2-6.4 mumol/kg) and caerulein dose range 0.1-0.8 mumol/kg) showed bell-shaped dose-effect curves, with the greatest maximum inhibition for CCK-8-NS. The peptide CCK-5-8 had weak anticonvulsant activity in comparison to the octapeptides, 3.2 mumol/kg and larger doses of the reference drug, diazepam, totally prevented picrotoxin-induced seizures and mortality. The maximum effect of the peptides tested was less than that of diazepam. Experiments with analogues and derivatives of CCK-5-8 demonstrated that the effectiveness of the beta-alanyl derivatives of CCK-5-8 were enhanced and that they were equipotent with CCK-8-SE. Of the CCK-2-8 analogues, Ser(SO3H)7-Ac-CCK-2-8-SE and Thr(SO3H)7-Ac-CCK-2-8-SE and Hyp(SO3H)-Ac-CCK-2-8-SE were slightly more active than CCK-8-SE.

Animals↗

The effects of beta-(Tyr9)melanotropin-(9-18) and H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on the analgesic action of morphine.

beta-(Tyr9)melanotropin-(9-18), which itself has no analgesic action, as measured by the tail-flick and hot-plate methods, decreased morphine-induced analgesia following intracerebroventricular injection. H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH heptapeptide, which has weak CRF-like activity, had no action on analgesia and was not able to modify morphine-induced analgesia. Compared with ACTH1-24, which in a subcutaneous dose of 100 micrograms/rat decreased morphine-induced analgesia, the same dose of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH was ineffective.

Adrenocorticotropic Hormone↗

Influence of Z-Prolyl-D-Leucine on alpha-MPT-induced catecholamine utilization in specific mouse brain nuclei.

The synethetic dipeptide Z-Prolyl-D-Leucine (Z-Pro-D-Leu) inhibits the development of tolerance to and dependence on morphine in mice. The possible mode of action of the dipeptide was studied by measuring the alpha-MPT-induced disappearance of noradrenaline (NA) and dopamine (DA) either by a spectrofluorimetric assay in major brain areas (lower brainstem, striatum) or by a radioenzymatic assay in specific brain nuclei. For the latter purpose, mouse brain nuclei containing mainly the cell body areas (nucl. tractus solitarii, locus coeruleus, substantia nigra, area tegmentalis ventralis) or some selected terminal projections (nucl. caudatus, nucl. accumbens, gyrus dentatus hippocampi, nucl. raphe dorsalis) of major NA- and DA-containing pathways were selected. In the lower brainstem studied as a whole, the dipeptide did not affect the utilization of either NA or DA. Analysis of the data on the NA utilization in specific brain nuclei, however, revealed that the dipeptide affected NA disappearance in some mesencephalic-limbic nuclei which receive noradrenergic innervation from the dorsal noradrenergic bundle (e.g., nucl. raphe dorsalis, area tegmentalis ventralis, gyrus dentatus). NA utilization in the cell body region of the same pathway (locus coeruleus), however, was not affected by the dipeptide. The dipeptide facilitated DA utilization in the main terminal area of the mesolimbic DA-ergic projection (nucl. accumbens), whereas the same treatment inhibited DA utilization in the main terminal region of the nigro-striatal DA-ergic pathway (nucl. caudatus). The data suggest that localized changes in NA and DA utilization following Z-Pro-D-Leu might be important for peptide-induced changes in morphine tolerance and dependence.

Animals↗

Effect of intracerebroventricular administration of beta-/Tyr9/-melanotropin-/9-18/ on rotational behavior induced by substantia nigra lesion in rats.

beta-/Tyr9/melanotropin-/9-18/ administered intracerebroventricularly /icv./ in doses of 1 microgram/rat or 10 micrograms/rat had no influence on the substantia nigra lesion-induced turning activity of rats, however, it was able to potentiate apomorphine-induced contralateral turning. In a dose of 20 micrograms/rat /icv./ the peptide alone induced clear contralateral turning. The results suggest that at lower doses the peptide facilitates apomorphine-induced dopamine receptor stimulation, while in a higher dose the peptide alone can stimulate dopamine receptor activity.

Amphetamine↗

The effects of interaction between propranolol and somatostatin on the active avoidance behavior, open-field activity and electroconvulsive shock-induced amnesia of rats.

In the present study the role of beta-receptors in the behavioral action of somatostatin was investigated. Somatostatin inhibited extinction of the active avoidance behavior. Propranolol alone had no action on this behavior but significantly inhibited the peptide-induced effect. In the open-field test somatostatin induced locomotor activation; propranolol did not influence this effect of the peptide. Somatostatin inhibited electroconvulsive shock-induced amnesia. Propranolol alone had no action in this test, but significantly decreased the antiamnesic effect of the peptide. These results suggest that the central beta-receptors play an important role in the behavioral action of somatostatin.

Amnesia↗

Effects of desglycinamide-arginine-vasopressin (DG-AVP) on memory processes in diabetes insipidus patients and non-diabetic subjects.

The effects of desglycinamide9-arginine8-vasopressin (DG-AVP) on memory processes have been studied in patients with central diabetes insipidus (DI) and in non-diabetic control patients. Acute im injection of DG-AVP improved some aspects of short-term memory. Subchronic intranasal administration of DG-AVP facilitated short-term memory more consistently and in addition improved long-term memory. DG-AVP increased the attention, but only in the non-diabetic subjects. The effects of DG-AVP on memory processes persisted after discontinuation of treatment. DG-AVP did not affect the parameters for water and electrolyte metabolism, blood pressure and pulse rate neither in DI nor in the control patients. Thus, the memory effects of DG-AVP are probably mediated by a direct action on the central nervous system.

Adolescent↗

Comparative studies with cyclic and linear somatostatin on active avoidance behaviour and open-field activity in rats.

The action of cyclic and linear somatostatin on active avoidance and open-field behaviour was investigated in rats. Both peptides inhibited the extinction of the avoidance behaviour and slightly but not significantly increased the intertrial activity (ITR). Both peptides increased ambulation and rearing activity in a dose related fashion, while the grooming and defecation rates were not changed. Since both peptides are capable of increasing the locomotor performance this action might contribute to the effect exerted on the extinction of active avoidance behaviour.

Animals↗

Effect on brain monoamines in the rat of substituted and protected analogues of the oxytocin fragment, prolyl-leucyl-glycinamide following N-terminal substitution by homoproline.

Prolyl-leucyl-glycinamide (PLG) and its substituted and protected analogues were tested on the steady-state level of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in various brain areas. The tripeptides were structurally modified at the N-terminal proline residue either by protection with benzoxycarbonyl (Z group) or by tertiary butyroxycarbonyl (BOC), or by substitution with homoproline (HPRO). C-terminal modification was performed by substitution of the amino group of glycine (GLY-NH2) by methylester (GLY-OMe). The parent molecule (PLG) increased the 5-HT content in the striatum and the NA and DA levels in the dorsal hippocampus. N-terminal protection by Z-group resulted in a loss of these effects. Striatal effects re-appeared if a methylester group was introduced in the C-terminal glycine. Substitution of the N-terminal with HPRO or that of the C-terminal amine group by OMe resulted in a tendency to increase the 5-HT level in the hypothalamus.

Animals↗

The effect of linear somatostatin on the active avoidance behaviour and open-field activity on haloperidol, phenoxybenzamine and atropine pretreated rats.

Somatostatin administered intracerebroventricularly inhibited the extinction of active avoidance behaviour. The dopamine receptor blocking agent haloperidol, the alpha 1-receptor blocker phenoxybenzamine and the muscarinic anticholinergic agent atropine inhibited the behavioural effect of the peptide. Furthermore, somatostatin increased the locomotor activity of the animals. Neither of these drugs influenced the effect of the peptide exerted on locomotor activity. The peptide was ineffective on other parameters of the open-field test while phenoxybenzamine decreased the defecation rate of the animals and this effect was not influenced by somatostatin. The results suggest that the catecholaminergic and the cholinergic system play an important role in the inhibition of extinction produced by somatostatin but these mechanisms to not have a role in the locomotor activity induced by the peptide.

Animals↗

A modified screening method for rapid simultaneous determination of dopamine, noradrenaline and serotonin in the same brain region.

A modification of previously published fluorimetric methods for brain noradrenaline (NA), dopamine (DA), and serotonin (5-HT) assay is presented in this paper. The modification improved the sensitivity to 5-HT and resulted in a less time-consuming and less expensive method for noradrenaline and dopamine determination. The assay can be used for simultaneous estimation of NA, DA and 5-HT as well as for turnover studies, utilizing catecholamine synthesis inhibition or monoaminoxidase inhibition.

Animals↗

Effect of intraventricular administration of glutaurine on norepinephrine, dopamine and serotonin turnover in different brain regions in rats.

The effect of glutaurine (gamma-L-glutamyl-taurine, Litoralon) was studied on dopamine, norepinephrine and serotonin turnover in the hypothalamus, mesencephalon, amygdala, septum, hippocampus, cortex and cerebellum following intracerebroventricular administration. Dopamine and norepinephrine turnover, measured by alpha-methyl-paratyrosine inhibition of catecholamine synthesis, increased in the cerebellum and the norepinephrine turnover in the hypothalamus. Serotonin turnover, measured by serotonin accumulation induced by the MAO inhibitor pargyline, decreased in the mesencephalon. There was no change in catecholamine or serotonin turnover in the amygdala, septum, hippocampus and cortex. The data suggested a highly selective action of glutaurine on brain transmitters in certain brain areas, especially in the cerebellum.

Animals↗

Effects of a new antidepressant drug on active avoidance behavior in rats. Comparative study with tricyclic antidepressants.

The effects of a new antidepressant drug, EGYT-475 (1-benzyl-4-(2'-pyridylcarbonyl)-piperazine) on the acquisition and extinction of conditioned avoidance behavior following short and long-term treatment were studied in rats. The effects were compared with those of amitriptyline, imipramine and desipramine. In a six-day acquisition period, EGYT-475 in a 200 mg/kg dose p.o facilitated the acquisition, while amitriptyline, imipramine and desipramine either had no effect or impaired the acquisition, depending upon the dose used. In a six-day extinction period, EGYT-475 delayed the extinction following either oral or intraperitoneal administration, while amitriptyline, imipramine, and desipramine in various doses facilitated the extinction. On prolonged treatment the delayed extinction was maintained even after 42 days in animals treated with EGYT-475. The results indicate that EGYT-475, in contrast to tricyclic antidepressants, does not impair the acquisition of avoidance conditioning but rather improves it while it does not facilitate the extinction of learned behavior but considerably delays it.

Amitriptyline↗

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↗

Histamine-stimulated prostaglandin synthesis in rat brain microvessels.

The histamine-sensitivity of prostacyclin and prostaglandin synthesis was investigated in isolated brain microvessels prepared from normal and hypoxic exercised rats. 10(-4) M histamine stimulated the in vitro synthesis of all components of arachidonate cascade. The chronic hypoxic exercise also resulted in an enhanced production of each fraction. Hypoxia and histamine showed an additive effect in the synthesis of PGE2 only. The possible molecular mechanism induced by hypoxia and histamine is discussed.

Animals↗

Selective attenuation of passive avoidance behaviour by microinjection of beta-LPH62-77 and beta-LPH66-77 into the nucleus accumbens in rats.

Various fragments of beta-lipotropin were micro-injected into the nucleus accumbens of free-moving rats and the effects on one-trial passive avoidance behaviour were studied. The following peptides were used: beta-endorphin (beta-LPH61-91), met-enkephalin (beta-LPH61-65), des-tyrosine-gamma-endorphin (DT gamma E, beta-LPH62-77), des-enkephalin-gamma-endorphin (DE gamma E, beta-LPH66-77), des-tyrosine-alpha-endorphin (DT alpha E, beta-LPH 62-76) and beta-LPH47-53(ACTH4-10). The gamma-type endorphins (DT gamma E and DE gamma E) were the only peptides which significantly attenuated passive avoidance behaviour when given in a 20 pg dose 1 hr before the 24-hr retention test. All the other peptides were ineffective. Microinjection of DT gamma E into the dentate gyrus of the dorsal hippocampus, on the other hand, was without effect on passive avoidance. The accumbens nucleus, therefore, is a preferential highly sensitive brain site for gamma-type endorphins. The attenuation of passive avoidance behaviour following systemic administration of these peptides might be the result of an interaction with this mesolimbic structure.

Animals↗

Prostacyclin and prostaglandin synthesis in isolated brain capillaries.

The synthesis of prostacyclin and prostaglandins was examined in isolated blood-free brain capillaries of guinea-pigs and rats using 1-14C-arachidonic acid as a precursor. The main prostaglandins synthesized by guinea-pig microvessels were prostaglandin D2 and prostaglandin E2. Substantially less prostaglandin F2 alpha or the prostacyclin stable metabolite, 6-oxo-prostaglandin F1 alpha was synthesized. Rat capillary prostaglandin distribution differed substantially from that of the guinea-pigs although the principle prostaglandin was also PGD2. Total prostaglandin conversion was greater in guinea-pig capillaries than in the rat. Norepinephrine stimulated the prostaglandin forming capacity of blood free cerebral microvasculature of guinea-pigs. Prostacyclin and prostaglandins could be involved in the activity dependent regulation of regional cerebral blood flow and permeability.

Animals↗

The interaction between beta-[Tyr9]melanotropin-(9-18), haloperidol and amphetamine in different behavior tests of rats.

The effects of beta-[Tyr9]melanotropin-(9-18) on the extinction of the active avoidance reflex in (dopamine receptor blocker) haloperidol-treated animals, and on the open-field activity in haloperidol and amphetamine-treated rats were studied. It was shown that a systemically given 100 microgram dose of the peptide, which had no action on the ambulation and rearing activity in the open-field test, could still delay the extinction of the active avoidance reflex. Haloperidol treatment was able to partially block the effects of the ICV administered beta-[Tyr9]melanotropin-(9-18) on both the extinction and open-field activity. After intracerebroventricular administration, the effect of the peptide on the open-field test was partially similar to that of amphetamine: it facilitated the ambulation and rearing activity, and (in contrast with amphetamine) was able to facilitate the grooming activity, even in the presence of amphetamine. The results suggest that dopaminergic innervation might play a mediating role in the effect of beta-[Tyr9]melanotropin-(9-18) on the extinction of the active avoidance reflex and open-field activity. The effect on the open-field activity differens in part from that of amphetamine.

Amphetamine↗