Biomedical subjects

L Vécsei

Publications and source records attributed to L Vécsei.

At least 19 recordsLinked to original sources

PubMed1992

Behavioral and pharmacological effects of centrally administered aminooxyacetic acid in rats.

In the present experiment unilateral intrastriatal injections of aminooxyacetic acid (1, 2.5, 5 mumol) to freely moving animals and pentobarbital-anesthetized rats produced contralateral jerks and dose-dependent mortality, but no barrel rotation. At 10-12 days there were no significant differences in exploratory activity, passive avoidance behavior, and elevated plus-maze test in aminooxyacetic acid-treated animals as compared with controls. However freely moving animals microinjected with aminooxyacetic acid (but not the pentobarbital-pretreated group) had impaired learning activity in an active avoidance conditioning test, and showed reduced striatal concentrations of substance P and GABA. Intrastriatal injections of aminooxyacetic acid therefore result in both acute and chronic behavioral changes which are attenuated by pentobarbital anesthesia.

Aminooxyacetic Acid↗

PubMed1992

[Kynurenine and its metabolites in nervous system diseases].

Kynurenine is a metabolite of the tryptophan-nicotine-amide-adenine-dinucleotide pathway. Recent preclinical and clinical data suggest that kynurenine and its metabolites (kynurenic acid, quinolinic acid) may play important role in the pathogenesis of neurological and other disorders (Huntington's disease, epilepsy, hypoxia, ulcus, hepatic and infectious diseases). Experimental data and theoretical considerations suggest that modification of kynurenine metabolism and influence of the concentrations of kynurenine metabolites may be useful therapeutic strategies in treatment of several disorders. This review is a summary of the pathobiochemical mechanisms and possible therapeutic strategies.

Humans↗

PubMed1992

Suboccipital cerebrospinal fluid and plasma concentrations of somatostatin, neuropeptide Y and beta-endorphin in patients with common migraine.

The somatostatin-like (SLI), the neuropeptide Y-like (NPY-LI), and the beta-endorphin-like (BE-LI) immunoreactivities of cerebrospinal fluid (CSF) obtained by suboccipital puncture, or plasma from patients suffering from common migraine or other neuropsychiatric disorders were analysed. The SLI concentration was tendentiously decreased in the migraine patients during the attack-free period compared to that of a 'mixed neuropsychiatric group'. During the migraine attack the level of SLI was further decreased. Similar alteration was found in the CSF BE-LI, while the BE-LI in the plasma showed only a tendentious decrease in common migraine patients. The NPY-LI did not change during the attack period in the CSF or plasma. These findings may indicate the possible role of somatostatin in the pathogenesis of common migraine, and support earlier observations that beta-endorphin is involved in the development in this disorder.

Adult↗

PubMed1992

Kynurenine and probenecid inhibit pentylenetetrazol- and NMDLA-induced seizures and increase kynurenic acid concentrations in the brain.

Kynurenine is a direct precursor of kynurenic acid, the only known endogenous antagonist of excitatory amino acid receptors in the brain. Kynurenine administered intraperitoneally (150, 450, 900 mg/kg) 2 h before pentylenetetrazol injection dose-dependently increased the time to seizures, the time to death and the survivorship of mice. Kynurenine dose-dependently increased the time to seizures and the time to death in mice with NMDLA-induced seizures. Kynurenine, 900 mg/kg, was equally efficacious to diazepam, 2 mg/kg. Probenecid dose-dependently increased the time to seizures, the time to death and the survivorship of mice with pentylenetetrazol-induced seizures. Probenecid had no significant effects on NMDLA-induced seizures, although the time to death was prolonged in the NMDLA 500 mg/kg group. Probenecid potentiated the effects of kynurenine in these tests. Both probenecid and kynurenine significantly increased kynurenine and kynurenic acid concentrations in mouse cerebral cortex and striatum. These findings suggest that kynurenine (metabolized to kynurenic acid) has anticonvulsant effects, and probenecid potentiates these effects in mice.

Analysis of Variance↗

PubMed1991

Comparative behavioral and pharmacological studies with centrally administered kynurenine and kynurenic acid in rats.

In the present study the effects of kynurenine and its metabolite kynurenic acid were compared in different behavioral and pharmacological tests. Kynurenic acid administered i.c.v. resulted in ataxia and stereotypy in a dose-dependent manner (0.025-1.6 mumol). Administration of 0.8 mumol of kynurenic acid resulted in sleeping and an approximate 25% mortality of the animals. At a dose of 1.6 mumol all of the animals died within 2-5 min from cardiorespiratory failure. One hour after lower doses of kynurenic acid the behavior of the rats appeared normal (neither stereotypy nor ataxia were observed in their familiar environemnt), but their exploratory activity (0.025-0.2 mumol) was significantly lower in a novel environment (open-field box) compared to the control group. Twenty four hours after the injection of kynurenic acid the exploratory activity of the animals did not differ from the control group. Kynurenine administered i.c.v. in equimolar doses did not result in stereotypy, ataxia, sleeping or mortality of the animals although, immediately after high doses short-lasting (1-2 min) immobility was observed. The rearing activity of the high dose kynurenine-treated animals was lower 1 h after injection, but this effect disappeared 24 h after the treatment. Post-trial injection of kynurenic acid (0.2 mumol) slightly, but not significantly, inhibited the learning ability of the rats in an active avoidance paradigm. Kynurenine administered in an equimolar dose had no effect on the speed of learning, but significantly attenuated the intertrial activity of the rats. Kynurenic acid (0.2 mumol, 0.4 mumol) did not significantly inhibit the passive avoidance latency of the animals after post-trial treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Comparative behavioral and neurochemical studies with striatal kainic acid- or quinolinic acid-lesioned rats.

In the present studies the effects of kainic acid (KA)- or quinolinic acid (QA)-induced striatal lesions were compared in different behavioral tests in rats. Both KA- and QA-lesioned animals had ipsilateral barrel-rotation (BR). The KA-lesioned rats, however, had contralateral, while the QA-lesioned rats had both ipsi- and contralateral turning activity. The KA-lesioned animals showed increased open-field activity as well as increased percentage of entries, and time spent in the open arms of Montgomery's conflict test. Learning of an active avoidance response was strongly inhibited by both striatal QA- or KA-induced striatal lesions. The QA-lesioned animals showed less pronounced behavioral changes than KA-lesioned animals in most of the tests, and had a smaller loss of body weight. There was no significant difference in the extent of the KA- and QA-induced substance P (SP) and GABA depletions in striatum, however, the depletions with QA lesions were slightly greater. These findings show that KA-induced striatal lesions produce more pronounced behavioral effects than QA lesions of similar size. It is possible that the differential effects of KA versus QA on striatal interneurons may result in its more marked behavioral effects.

Animals↗

PubMed1991

Long-term effect of immunization with neural and nonneural antigens on the noradrenaline and serotonin levels of discrete brain areas in mice and the relationship between neurotransmitter levels and antibody production.

The effect of immunization with neural and nonneural antigens on hypothalamic and mesencephalic neurotransmission and antibody response have been investigated. Treatment of SJL/N mice with bovine myelin basic protein (BMBP), mouse spinal cord homogenate (MSCH) or bovine serum albumin (BSA) produced no significant changes in the average hypothalamic and mesencephalic noradrenaline (NA) or serotonin (5-HT) content. In Balb/c mice, however, treatment with BMBP caused a significant increase in mesencephalic NA, and treatment with MSCH caused a significant increase in hypothalamic 5-HT 3 weeks after the first antigenic challenge. The SJL/N strain showed a high antibody response to BMBP and BSA, and a moderate one to MSCH, while in Balb/c mice, there was a low response to BMBP, a moderate one to MSCH and a high response to BSA. Significant, positive correlations were found between the level of antigen-specific serum antibodies and the following neurotransmitters: hypothalamic NA in the BMBP and MSCH-treated groups, hypothalamic 5-HT in the MSCH-treated group, mesencephalic NA and 5-HT in the BMBP-treated group, and mesencephalic 5-HT in the MSCH-treated SJL/N animals. No significant correlations between the levels of antibodies and neurotransmitters have been found either in the BSA-immunized SJL/N animals, or in any of the groups of Balb/c mice treated with BMBP, MSCH or BSA.

Animals↗

PubMed1990

Influence of kynurenine treatment on open-field activity, elevated plus-maze, avoidance behaviors and seizures in rats.

In the present studies the effects of single and daily repeated injections of kynurenine were investigated in different behavioral tests in rats. In open-field behavior a single injection of kynurenine decreased rearing activity, while the effect was more pronounced after repeated injections. Similarly, in the elevated plus-maze, kynurenine attenuated the total number of entries in the four arms of the equipment, and after chronic treatment decreased the time spent in the open arms (control: 24%; kynurenine 100 mg/kg: 16%; kynurenine 200 mg/kg: 13%). Kynurenine did not influence the passive avoidance learning paradigm (learning session and avoidance latency) and the extinction of active avoidance response. Kynurenine slightly attenuated the kainic acid-induced wet dog shakes and forelimb clonic activity with rearing. These findings suggest that kynurenine (especially after repeated peripheral injections) inhibited several behavioral responses of the experimental animals. However, in one type of highly motivated experimental paradigm (fear from the foot shock), behavioral depression was not detectable.

Animals↗

PubMed1990

Dose- and time-response effects of pantethine on open-field behavior, and on central neurotransmission in rats.

In this study the dose- and time-related effects of pantethine on open-field behavior and central neurotransmissions were investigated in rats. Pantethine administered in low doses (0.48-0.96 mM/kg SC) only marginally influenced the activity of the animals, but induced a significant decrease of hypothalamic noradrenaline level without influencing the concentrations of dopamine and DOPAC. Injected in higher doses (1.95-3.90 mM/kg SC), the compound produced a marked depression of both open-field activity and noradrenaline levels, but increased the concentrations of dopamine and DOPAC in the hypothalamus. Twelve hr after the administration of the substance, its effect was attenuated, and 24 hr after the treatment neither the behavioral nor the monoamine parameters differed significantly from the control values. Concerning the somatostatin, pantethine administered in high doses (1.95-3.90 mM/kg SC) decreased the striatal concentration of somatostatin 4 hr after the injection, and this effect was attenuated 24 hr after the treatment. These data suggest that the pantethine-induced behavioral changes are correlated with its effect on central catecholaminergic and somatostatinergic transmission.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Somatostatin28(15-28), but not somatostatin28(1-12), affects central monoaminergic neurotransmission in rats.

The effects of intracerebroventricularly (icv) administered somatostatin28(SS28) fragments, SS28(1-12) and SS28(15-28), were investigated on central monoaminergic neurotransmission in rats. SS28(15-28) did not significantly influence the hypothalamic and striatal noradrenaline concentrations. In a dose-related manner, SS28(15-28) significantly increased the dopamine, dihydroxyphenyl acetic acid DOPAC), and serotonin concentrations in hypothalamus, but did not modify these measures in striatum. The other SS28 metabolite, SS28(1-12), had no statistically significant effects on the monoamine neurotransmission. SS28(15-28) (6 and 9 nmol) induced barrel rotation, while SS28(1-12) was ineffective following administration over a wide dose-range (3-18 nmol). In conclusion, SS28(15-28) influences the hypothalamic monoaminergic transmission and causes barrel rotation, whereas SS28(1-12) has no neurochemical or behavioural effects in these tests.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Preclinical and clinical studies with somatostatin related to the central nervous system.

1. The tetradecapeptide somatostatin (SS) has a widespread, uneven distribution within several organs including the central nervous system (CNS), with particularly high concentration in the hypothalamus. 2. The SS-related peptides (SS28, SS28(1-12), SS28(15-28)) are originated from the precursor pre-prosomatostatin. 3. SS is suggested to be involved in a large number of CNS functions, locomotion, sedation, excitation, catatonia, body temperature, feeding, nociception, paradoxical sleep, self-stimulation, seizure, learning and memory. 4. SS influences central neurochemical processes. 5. It is possible that SS is related to various neurological and psychiatric illnesses, like Huntington's disease, multiple sclerosis, Parkinson's disease, epilepsy, eating disorders, Alzheimer's disease, schizophrenia and major depressive illness.

Animals↗

PubMed1990

Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system.

1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactin-secreting adenomas) indications in clinical practice. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed.

Alcoholism↗

PubMed1990

Effects of somatostatin-28 and some of its fragments and analogs on open-field behavior, barrel rotation, and shuttle box learning in rats.

The effect of intracerebroventricular (ICV) administration of somatostatin-28 (SS-28) and some of its fragments, SS-28 (1-12), SS-28(15-28), and analogs, des-AA-(1,2,4,5,12,13)-(DTrp8)SS-14, ODT8-SS, and (DTrp8,DCys14)SS-14 were studied in different behavioral tests on rats. SS-28 (6.0 nM) decreased, SS-28(15-28) (0.6 nM) increased, and SS-28(15-28) (6.0 nM) decreased activity of the animals in an open-field test. SS-28(1-12) (0.6, 3.0, and 6.0 nM) did not influence this behavior. ODT8-SS (0.6, 3.0, and 6.0 nM) decreased activity of the rats, while (DTrp8,DCys14)SS-14 increased it, only at a high dose (6.0 nM). Similar results were obtained for barrel rotation, except that (DTrp8,DCys14)SS-14 even in high dose (12.0 nM) had no effect. In a shuttle-box learning paradigm, SS-28(15-28) (0.6 nM) facilitated, while SS-28(1-12) (0.6 nM) did not influence, the performance of the animals. These results suggest that the isomeric Cys(28) form of the SS-28(15-28) molecule may be crucial for the expression of the behavioral effects of these peptides.

Amino Acid Sequence↗

PubMed1990

Intracerebroventricular injection of kynurenic acid, but not kynurenine, induces ataxia and stereotyped behavior in rats.

In the present studies the behavioral-pharmacological effects of kynurenine and its metabolite kynurenic acid were investigated after intracerebroventricular (ICV) microinjection in rats. Kynurenine (0.1 and 0.2 mumol ICV) produced slight behavioral changes, but its metabolite kynurenic acid (0.2 mumol ICV) induced marked ataxia, stereotyped behavior and muscular hypotonia in a dose-dependent manner. The kynurenic acid-induced neurological symptoms were partially inhibited but not eliminated by ICV pretreatment with D-serine (0.5, 2.5, 5 mumol), which is a selective agonist at the strychnine-insensitive glycine binding site of the NMDA-receptor complex. Our results support the following conclusions: 1) kynurenine (0.1 or 0.2 mumol, ICV) results in slight stereotypy and ataxia, but the speed of its metabolism to kynurenic acid in this paradigm is not sufficient to produce concentrations of kynurenic acid, which are able to elicit marked ataxia and stereotypy; 2) the duration of kynurenic acid-induced behavioral abnormalities is correlated with the length of disappearance of micro-injected kynurenic acid from brain tissue; 3) D-serine which is an agonist at the glycine site linked to the NMDA complex, partially antagonizes but does not eliminate the neurological disturbances induced by ICV kynurenic acid injection.

Animals↗

PubMed1990

Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis.

The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

Adult↗

PubMed1990

Non-specific peroxidase (donor: H2O2-oxidoreductase, EC 1.11.1.7) activity in multiple sclerosis.

The non-specific peroxidase (donor: H2O2-oxidoreductase, EC 1.11.1.7) activity of red blood cells in patients with multiple sclerosis, patients with other neurological diseases, and healthy control individuals was investigated. To this end, a simple method was developed. No significant difference was found in the non-specific peroxidase activity of red blood cells from patients with multiple sclerosis and controls.

Adult↗

PubMed1989

Influence of cysteamine and cysteine on open-field behaviour, and on brain concentrations of catecholamines, somatostatin, neuropeptide Y, and corticotropin releasing hormone in the rat.

Cysteamine (1.95 or 3.90 mM/kg) administered subcutaneously (sc) markedly decreased the open-field activity of the rats, while the structurally related amino acid cysteine had only minor influence. Cysteamine (1.95 or 3.90 mM/kg) reduced the noradrenaline and increased the dopamine and dihydroxyphenyl acetic acid (DOPAC) levels in the hypothalamus. In striatum the drug decreased both the noradrenaline (1.95 or 3.90 mM/kg) and dopamine (3.90 mM/kg) levels without influencing the DOPAC content. Neither the hypothalamic nor the striatal catecholamines are influenced by administration of equimolar doses of cysteine. Cysteamine (1.95 or 3.90 mM/kg) decreased the somatostatin levels both in the hypothalamus and in the striatum without influencing neuropeptide Y (NPY) and corticotropin releasing hormone (CRH) concentrations. Cysteine administered in equimolar doses did not influence the peptide levels in these brain structures. These data suggest that the cysteamine-induced behavioural changes are related to the decrease of brain noradrenaline and somatostatin concentrations. The structurally related amino acid cysteine does not influence the behaviour or the central monoaminergic and peptidergic concentrations in the hypothalamus and striatum of rats.

Animals↗

PubMed1989

Effects of cysteamine and pantethine on open-field behavior, hypothalamic catecholamine concentrations, and somatostatin-induced barrel rotation in rats.

Cysteamine administered in a dose of 1.95 mM/kg subcutaneously (SC) markedly reduced several open-field behaviors (locomotion, rearing, grooming and defecation), while pantethine, administered in an equimolar dose, reduced the locomotion only. However, administered in a dose of 3.90 mM/kg (SC), pantethine also markedly reduced all open-field parameters. Cysteamine, and to less extent pantethine, reduced noradrenaline, and increased dopamine and DOPAC concentrations in the hypothalamus. It is discussed whether the lower potency of pantethine on open-field behaviors and hypothalamic catecholaminergic neurotransmission is connected with the limited activity of pantetheinase, the cysteamine-generating enzyme. Intracerebroventricularly (ICV) administered somatostatin did not influence the pantethine-induced (1.95 mM/kg SC) behavioral changes in the open-field test. It is possible that the peptide did not reach at the receptor sites in a sufficient concentration because of the reduced endogenous somatostatin content, or that the pantethine-induced noradrenaline depletion is connected with the ineffectiveness of somatostatin. Furthermore, pretreatment with cysteamine (1.95 mM/kg SC) or pantethine (1.95 mM/kg or 3.90 mM/kg SC) attenuated the somatostatin-induced (10 micrograms ICV) barrel rotation, suggesting that the level of endogenous somatostatin may play a role in the pathogenesis of this motor disturbance.

Animals↗