Biomedical subjects

G Telegdy

Publications and source records attributed to G Telegdy.

At least 181 records · Page 10Linked to original sources

PubMed1984

Inhibition of seizures induced by picrotoxin and electroshock by cholecystokinin octapeptides and their fragments in rats after intracerebroventricular administration.

The anticonvulsive activity of cholecystokinin octapeptide sulphate ester (CCK-8-SE), non-sulphated cholecystokinin octapeptide (CCK-8-NS) and three different N- and C-terminal fragments were investigated against seizures induced by picrotoxin and electroshock in rats after intracerebroventricular administration. Doses of 0.8 and 80 pmol of CCK-8-SE and CCK-8-NS significantly enhanced the latency of seizures induced by picrotoxin and shortened the duration of the clonic phase of the seizures induced by electroshock. Only CCK-8-SE shortened the recovery time and only 0.8 pmol of CCK-8-SE could shorten the duration of the tonic phase of convulsions induced by electroshock. Doses of the octapeptides of 8000 pmol were ineffective, with the exception of CCK-8-NS in the picrotoxin test. Of the fragments tested, the C-terminal tetrapeptide, CCK-5-8, enhanced the latency of seizures induced by picrotoxin in a dose of 0.8 pmol, and had a dose-dependent biphasic effect on the duration of the clonic phase of seizures induced by electroshock. Intracerebroventricular administration of diazepam enhanced only the latency of tremor and clonic seizures induced with picrotoxin in a dose of 40 nmol. Twelve nmole of diazepam shortened the clonic phase of convulsions induced by electroshock. The peptides tested were much more active than diazepam, and their effective doses were comparable to the amounts of cholecystokinin octapeptide found in brain structures.

Animals↗

PubMed1984

Effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on the in vitro uptake and release of radiolabelled dopamine, noradrenaline and serotonin in rat brain hypothalamic slices.

The effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH, a hypothalamic heptapeptide with weak CRF activity were investigated on the in vitro uptake and release of radiolabelled dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in rat brain hypothalamic slices. In a doses of 5 X 10(-6) M and 10(-5) M the heptapeptide significantly increased the 5-HT uptake, whereas it had no effect on the DA and NA uptakes. The same doses (5 X 10(-6) M, 10(-5) M) significantly increased the DA release without affecting the NA and 5-HT release. These results suggest that H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH as a hypothalamic peptide is able to modulate selectively the activity of the serotonergic and dopaminergic transmission without influencing the noradrenergic system in the hypothalamus.

Animals↗

PubMed1984

The effects of sulfated and nonsulfated cholecystokinin octapeptides on electroconvulsive shock-induced retrograde amnesia after intracerebroventricular administration in rats.

The effects of several doses of intracerebroventricularly injected cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated scholecystokinin octapeptide (CCK-8-NS) were studied on electroconvulsive shock (ECS)-induced retrograde amnesia, as measured in a one-trial step-through passive avoidance paradigm. Both CCK-8-SE and CCK-8-NS were able to attenuate amnesia slightly when they were injected into rats 10 min prior to ECS treatment, possibly by reducing the severity of the ECS-induced seizures. Of the treatments carried out immediately after ECS, only the 0.8 pmole dose of CCK-8-NS could significantly restore retrograde amnesia. After treatment 20 min prior to testing 24-hr retention, no effect of the peptides was observed. The lack of a dose-dependency and of any effect on retrieval raises the possibility that the CCK octapeptides influence memory processes by an indirect mechanism.

Amnesia↗

PubMed1984

The effects of somatostatin, its fragments and an analog on electroconvulsive shock-induced amnesia in rats.

In the present study the effects of intracerebroventricularly [icv] administered somatostatin [linear and cyclic], somatostatin3-6, somatostatin7-10 and des AA1,2,4,5,12,13 [D-Trp8] somatostatin [ODT8-SS] were investigated on electroconvulsive shock [ECS]-induced retrograde amnesia in rats. The ECS significantly decreased the foot shock-induced avoidance latency, and thus caused retrograde amnesia. Somatostatin [linear and cyclic] in a dose of 0.6 nM had no action on the ECS-induced retrograde amnesia, while in doses of 3 nM and [cyclic only] 6 nM it significantly prevented it. Somatostatin3-6, somatostatin7-10 and ODT8-SS in doses of 0.6, 3 and 6 nM had no effect on the ECS-induced amnesia. These results indicate that the whole sequence of the original somatostatin molecule is needed to block the ECS-caused retrograde amnesia.

Amnesia↗

PubMed1984

The influence of oxytocin on the steady-state level and accumulation of serotonin in rat brain regions.

The effects of graded amounts of centrally injected [intracerebroventricular, i.c.v.] oxytocin [OXT] have been studied on the steady-state level and pargyline-induced accumulation of serotonin [5-HT] in the hypothalamus, mesencephalon and dorsal hippocampus of rats. OXT only weakly affected the steady-state level of 5-HT. The pargyline-induced accumulation, on the other hand, was inhibited by central OXT treatment. Whereas OXT inhibited 5-HT accumulation in a dose-dependent manner in the hypothalamus, only the lowest amount of OXT was effective in the mesencephalon and the dorsal hippocampus. The data raise the possibility that an altered 5-HT metabolism is likely to have functional significance in the endocrine and behavioral effects of OXT.

Animals↗

PubMed1984

Effects of oxytocin and a derivative (Z-prolyl-D-leucine) on morphine tolerance/withdrawal are mediated by the limbic system.

Recent data indicate that the neurohypophyseal hormone oxytocin (OXT) and Z-prolyl-D-leucine (Z-Pro-D-Leu), a synthetic dipeptide derived from the C-terminal part of OXT, attenuate the development of tolerance to and dependence on morphine in the mouse. Biochemical and behavioral data raise the possibility that these effects of the peptides might be associated with their effects on the central nervous system and in particular on limbic brain structures. The present results confirm this hypothesis, since intracerebroventricular (i.c.v., 50 ng) and local (0.5 ng) injections of OXT and Z-Pro-D-Leu into the dorsal hippocampus and the mesolimbic nucleus accumbens attenuate morphine tolerance/dependence, similarly to systemic injections of these peptides in higher amounts (5-50 micrograms). Local injections of these peptides into other brain sites (e.g. the nucleus caudatus, ventral tegmental area and the external cortical surface) are without effect. Lesion of the nucleus accumbens by the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) completely prevents the effects of Z-Pro-D-Leu and partially those of OXT on morphine tolerance/dependence. The data point to the role of limbic structures as mediators of the effects of neuropeptides on morphine addiction.

Animals↗

PubMed1984

Increased sensitivity to picrotoxin as an index of physical dependence on alcohol in the mouse.

A relatively simple and rapid method has been developed to induce tolerance to and dependence on alcohol in mice. Alternating intraperitoneal injections of metabolically stable tert-butanol and ethanol for 4 consecutive days resulted in a physical dependence on alcohol, which was quantified by the latency and ED50 of picrotoxin-induced CNS hyperexcitability--myoclonic and tonic seizures and mortality--during the withdrawal period. The data indicate that alcohol-dependent animals in the withdrawal period are more susceptible than alcohol-naive controls to picrotoxin. Withdrawal hyperexcitability can be quantified by the ED50 of picrotoxin.

Alcohol Withdrawal Delirium↗

PubMed1984

The effect of beta-(Tyr9)melanotropin-(9-18) on the active avoidance and open-field behavior on rats pretreated with atropine or propranolol.

beta-(Tyr9)melanotropin-(9-18) inhibited the extinction of active avoidance behavior. The muscarinic cholinergic blocker atropine did not influence the peptide-induced inhibition, whereas the beta-receptor blocker propranolol decreased it. Furthermore, the peptide increased the ambulation of the animals. Neither the muscarinic blocker nor the beta-blocker had any action on this effect of beta-(Tyr9)melanotropin-(9-18). Atropine markedly decreased the defecation of the animals, and this effect was not influenced by the peptide. The results suggest that the beta-receptors play an important role in the inhibition of extinction induced by the peptide, however, the actions on the open-field activity are mediated by different mechanisms.

Animals↗

PubMed1984

Comparative studies with beta-(Tyr9)melanotropin-(9-18) and amphetamine on open-field behavior and striatal dopamine uptake and release.

The effect of beta-(Tyr9)melanotropin-(9-18) and amphetamine on the open-field behavior and the striatal dopamine uptake and release were compared. beta-(Tyr9)melanotropin-(9-18) at doses of 1 microgram (icv) or 2 micrograms (icv) increased the ambulation of the rats, while in a dose of 5 micrograms (icv), it had no effect. Amphetamine had a similar dose-related effect on ambulation. This peptide also increased the rearing activity, in doses of 2 micrograms or 5 micrograms (icv), while amphetamine was effective only in a dose of 2 micrograms (icv). beta-(Tyr9)melanotropin-(9-18) at doses of 1 microgram, 2 micrograms or 5 micrograms (icv) increased the grooming, while amphetamine at the same doses decrease it. The peptide had no significant influence on the striatal dopamine uptake and release, whereas amphetamine markedly decreased the uptake and facilitated the release in a dose-related manner. These results suggest that although beta-(Tyr9)melanotropin-(9-18) and amphetamine have similar effects on the open-field behavior, the mechanisms of action of the two substances are different.

Amphetamine↗

PubMed1984

Comparative studies with somatostatin and cysteamine in different behavioral tests on rats.

In the present study the effects of somatostatin and cysteamine (a selective decreaser of the somatostatin level in the body) were compared in different behavioral tests on rats. Somatostatin inhibited the extinction of active avoidance behavior 8 hr and 24 hr after intracerebroventricular (ICV) treatment, while cysteamine facilitated it 4 hr and 8 hr after subcutaneous (SC) treatment. Somatostatin did not significantly influence the cysteamine-induced facilitation of the extinction. Somatostatin did not have a significant effect on T-maze spatial discrimination learning and reverse learning, whereas cysteamine markedly attenuated the performance 4 hr (1st day) after treatment. Somatostatin in a dose of 4 micrograms (ICV) increased the locomotor activity 10 min after treatment, while cysteamine markedly decreased all parameters of the open-field test. These effects of the drug had disappeared 24 hr after treatment. If different doses of somatostatin (4 micrograms or 10 micrograms ICV) were administered to cysteamine-pretreated rats, the peptide did not modify the drug-induced changes in the open-field test. The data suggest that the brain somatostatin might have a physiological role in the organization of certain types of behavior.

Animals↗

PubMed1984

Changes in brain monoamine levels of rats during cholecystokinin octapeptide-induced suppression of feeding.

Cholecystokinin octapeptide (CCK-8) in doses of 5 or 10 micrograms/kg was injected intraperitoneally to 24 hr food-deprived rats before a 30 min feeding period, and the dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT) contents of the hypothalamus, mesencephalon, amygdala, hippocampus and striatum were measured thereafter. The experimental procedure (deprivation + food intake) alone could induce changes in the brain monoamine contents of saline-treated animals as compared to the nondeprived control group. The most striking effect was observed in the hypothalamus, in which the contents of all three monoamines decreased. In the deprived control group there was a significant positive correlation calculated by linear regression analysis between the amount of food eaten and the DA contents of the amygdala. Injection of CCK-8 before food intake testing decreased the DA contents of the hypothalamus. In the CCK-8-treated animals the correlation between food intake and amygdaloid DA contents disappeared. The CCK-8 treatment specifically gave rise to a significant positive correlation between the amount of food eaten and the NE content of the hypothalamus; such a relation could not be observed in the saline-treated group. The hypothalamic NE contents altered in parallel with the effectiveness of both doses of CCK-8 in inhibiting food intake. The results indicate the importance of the hypothalamic NE system in the food intake-suppressing effect of CCK-8.

Animals↗

PubMed1984

Drugs affecting brain dopamine interfere with the effect of Z-prolyl-D-leucine on morphine withdrawal.

The dipeptide Z-prolyl-D-leucine (Z-Pro-D-Leu) has been demonstrated to inhibit the development of tolerance to and dependence on morphine in the mouse. Since the dipeptide affects dopamine (DA) utilization in the terminal regions of the mesolimbic and nigrostriatal DA-ergic projections, the question has been studied of whether DA-ergic mechanisms are involved in the action of Z-Pro-D-Leu on morphine withdrawal. Both inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine (alpha-MPT) and inhibition of DA receptors by pimozide interfere with the effect of Z-Pro-D-Leu on naloxone-precipitated morphine withdrawal. Inhibition of serotonin (5-HT) synthesis by DL-p-chlorophenylalanine (PCPA), on the other hand, does not modify the effect of the dipeptide. The results argue for a role of DA-ergic mechanisms in the effect of Z-Pro-D-Leu on the development of morphine dependence.

Animals↗

PubMed1984

Synthesis of potent heptapeptide analogues of cholecystokinin.

Nine new analogues of acetyl-CCK-heptapeptide (Ac-Tyr(SO3H)2-Met3-Gly4-Trp5-Met6-Asp7-Phe8-NH2 ) were synthesized by solid-phase methodology. In a first series, the Asp7 residue was replaced by hydroxy amino acid sulfate esters. In another series, Gly4 was substituted by D-Ala, while Trp5 and Met6 were replaced by their D enantiomer. The introduction of the sulfate ester was performed with a new, mild, crystalline, and stable reagent, pyridinium acetyl sulfate. Each analogue that contained Tyr(SO3H)2 and a hydroxy amino acid sulfate ester [Ser(SO3H), Thr(SO3H), or Hyp(SO3H)] in position 7 proved to be more potent (1.9, 1.7, and 3.0 times, respectively) than CCK-8 in vitro (isolated gallbladder strips). While devoid of gastrin-like activity in vivo, these analogues had potent anticonvulsive activity. The analogues containing a D-amino acid residue were less potent than the parent compound in vitro. The D-Ala4 replacement, however, yielded a compound that was 40% as potent as CCK-8 in the in vitro test but showed prolonged duration of action on sphincter Oddi. While the 7-substituted Ac-CCK heptapeptides are among the most potent CCK analogues reported so far, the D-Ala4 replacement resulted, for the first time, in prolonged activity in vivo.

Amino Acid Sequence↗

PubMed1984

Effect of somatostatin and its fragments on turning behaviour induced by unilateral substantia nigra lesion in the rat.

The effect of somatostatin and its two tetrapeptide fragments was investigated on turning activity induced by unilateral substantia nigra lesion in rats. Somatostatin in a dose of 0.6 nM had no action on the turning behavior, while a dose of 6 nM increased slightly while a dose of 12 nM significantly the contralateral turning. Cys-Lys-Asn-Phe and Phe-Trp-Lys-Thr had no action in low or high doses on the turning activity of the animals. The results suggest that somatostatin has a direct postsynaptic dopamine receptor stimulating effect. It seems that for dopamine receptor stimulating action the complete somatostatin molecule is needed.

Amphetamines↗

PubMed1984

Dipeptides delay the onset of morphine withdrawal in the mouse.

The effect of dipeptides was studied on naloxone-precipitated morphine withdrawal in the mouse. In accordance with previous data, s.c. treatment with Z-prolyl-D-leucine delayed the onset of withdrawal jumpings . Replacement of L-proline by L-glutamate or L-pyroglutamate resulted in dipeptides which were more potent in morphine withdrawal than was Z-prolyl-D-leucine.

Analysis of Variance↗

PubMed1983

Catecholamine utilization in distinct mouse brain nuclei during acute morphine treatment, morphine tolerance and withdrawal syndrome.

The steady-state levels and utilization (alpha-MPT-induced disappearance) of noradrenaline (NA) and dopamine (DA) were measured in distinct mouse brain nuclei after acute morphine challenge, in mice rendered tolerant to morphine, and during the naloxone-precipitated morphine withdrawal syndrome. Mouse brain nuclei containing mainly the cell body areas and some terminal projections of major NA- and DA-containing pathways were selected (nucleus tractus solitarii, locus coeruleus, substantia nigra, area tegmentalis ventralis and nucleus caudatus, nucleus accumbens, gyrus dentatus hippocampi, nucleus raphe dorsalis respectively). Acute morphine treatment reduced the utilization of NA in all brain nuclei but the substantia nigra. In morphine-tolerant mice, all changes characteristic for acute morphine treatment disappeared. Instead, an increased NA utilization was observed in the nucleus tractus solitarii and the area tegmentalis ventralis in the tolerant animals. During morphine withdrawal, an abrupt decrease was observed in the utilization of NA in the nucleus tractus solitarii, whereas the NA utilization in the gyrus dentatus abruptly increased, as compared to the tolerant state. Acute morphine challenge decreased the utilization of DA in the nucleus caudatus, locus coeruleus and nucleus raphe dorsalis. In the tolerant mouse, an increased utilization of DA was observed in the nucleus tractus solitarii. During morphine withdrawal, DA utilization was decreased in the substantia nigra and the area tegmentalis ventralis, while in the nucleus accumbens withdrawal resulted in an increase of DA utilization. The data suggest that acute effects of morphine as well as morphine tolerance/dependence are accompanied by, and likely to be associated with, distinct changes in the catecholamine metabolism of specific mouse brain nuclei.

Animals↗

PubMed1983

Effect of cholecystokinin on self-stimulation behavior in rats.

Experiments were performed to examine the effects of intracerebroventricularly administered cholecystokinin octapeptide sulfate ester (CCK-8-SE) and unsulfated cholecystokinin octapeptide (CCK-8-NS) on electrical self-stimulation behavior elicited from the medial forebrain bundle. CCK-8-SE and CCK-8-NS in 80 pmol doses reduced the response rate of self-stimulation behavior 22-30 min following injection, while 400 pmol doses of these peptides attenuated self-stimulation behavior between 13 and 36 min. It is suggested that CCK-8-SE and CCK-8-NS interact with central rather than peripheral nervous mechanisms.

Animals↗

PubMed1983

The effect of somatostatin on self-stimulation behavior in atropine- and methysergide-pretreated rats.

The effect of somatostatin on lateral hypothalamic self-stimulation was investigated in atropine- and methysergide-pretreated rats. Somatostatin markedly decreased the self-stimulation rate of the animals. Atropine in a dose which had no action on self-stimulation partly antagonized the effect of somatostatin. Methysergide potentiated the somatostatin-induced depression of self-stimulation behavior. These results suggest that the central cholinergic and serotoninergic systems may play a role in the somatostatin-induced inhibition of self-stimulation.

Animals↗