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Biomedical subjects

G L Kovács

Publications and source records attributed to G L Kovács.

At least 19 recordsLinked to original sources
PubMed2005

Minor disturbances in central nervous system function in familial neurohypophysial diabetes insipidus.

Familial neurohypophysial diabetes insipidus (FNDI) is caused by a defect in vasopressin synthesis and release as a result of a heterozygous mutation in the gene for the vasopressin prohormone. The predominant characteristic of FNDI is excessive thirst and urine production. However, vasopressin not only has peripheral endocrine effects, but also regulates numerous brain functions. We investigated whether central functions are affected in FNDI, by studying neuropsychological functioning of 23 affected members (15 males, 8 females) of a large family carrying a T/G transition mutation at nucleotide 2110 (codon 116) of the vasopressin prohormone gene (Cys116Gly). The relatively large number of family members with FNDI made it possible to compare cognitive and other CNS effects in these subjects with those of family members without FNDI. Thirty-seven adult volunteers (20 males, 17 females) from the same family and 11 non-family members (2 males, 9 females) from northern part of The Netherlands were tested. The mean age of the subjects was 35+/-12 years. Of the 63 quantified neuropsychological parameters few were statistically different between the subjects with FDNI and control subjects. Memory retrieval processes and sustained attention were worse in the subjects with FDNI. Moreover, these individuals reported significantly fewer symptoms of agoraphobia and miscellaneous symptoms, and had significantly lower scores on a scale measuring anger. The performance of FNDI subjects on an auditory verbal learning test (the 15-word test learning trial) was worse, but not significantly so, than that of the subjects without FDNI. There were subjective complaints of forgetfulness and slow recalls and those were observed in daily life by non-affected family members. These moderate differences in neuropsychological performance indicate that in human FNDI parvocellular vasopressin systems that supply the brain may be less affected or give no such serious disabilities, than the magnocellular hypothalamo-neurohypophysial system that provides vasopressin for endocrine regulation of water homeostasis.

Adult↗
PubMed2004

Comparative analytical evaluation of thyroid hormone levels in pregnancy and in women taking oral contraceptives: a study from an iodine deficient area.

Increase of serum thyroxine binding globulin (TBG) resulting from estrogen action may lead to problems in thyroid diagnostics. The aim of the present study was to define the most diagnostically reliable thyroid parameters in women exposed to differentially elevated estrogens. Sera of three groups of healthy women were analyzed: women taking no medicine (controls), those taking oral contraceptives and pregnant women (in weeks 16 or 32 of gestation). All women involved in the study lived in a moderately iodine-deficient geographical area. Thyroid stimulating hormone (TSH), TBG, total thyroxine (T4), total tri-iodothyronine (T3) and free T3 were determined and free T4 indices (total T4 x T3 uptake; total T4/thyroxine binding capacity (TBC); total T4/TBG) were calculated. Free T4 was measured simultaneously with a one-step T4-analog enzyme-linked immunosorbent assay (ELISA), a labeled T4 antibody radioimmunoassay (RIA), and a two-step microparticle enzyme immunoassay (MEIA). Estrogen-dependent differences were found in all investigated parameters; however, they remained in the reference interval for TSH, total T4 x T3 uptake, total T4/TBC,free T3 and free T4 MEIA. It was concluded that simultaneous estimations of free T4 and free T3 should follow a primary TSH measurement. The necessity of a distinct reference range has emerged for free thyroid hormones in midterm and late pregnancy as well as in the use of oral contraceptives, especially in iodine-deficient areas.

Adult↗
PubMed2003

Natriuretic peptides in alcohol withdrawal: central and peripheral mechanisms.

Abrupt cessation of long-term alcohol consumption produces well-defined symptoms called alcohol withdrawal (AW). The exact pathophysiological mechanisms involved in the appearance of AW symptoms and particularly those related to the precipitation of delirium tremens (DT), still await clarification in spite of the fact that the prediction of complicated AW is essential to guarantee that appropriate therapies may be planned in advance. Changes in central nervous system (CNS) glutamate- and GABA-transmission and a role of voltage-operated calcium channels are equally important elements of neuroadaptation to the chronic presence of alcohol. In addition to the CNS regulation, however, changes in peripheral fluid and electrolyte homeostasis may accompany, and are expected to modify the clinical symptoms of AW. In an early phase of acute withdrawal, plasma levels of atrial natriuretic peptide (ANP), plasma renin activity and aldosterone are high. In patients with DT, elevated levels of ANP were observed days before the actual onset of DT. It is concluded that the altered plasma ANP secretion might be associated with, and therefore used as an indicator of the onset of DT. However, ANP is present in and produced by the brain and thus it can be regarded as a neuropeptide. The role of CNS ANP was studied in mice, rendered tolerant to and physically dependent on alcohol. Intracerebroventricular injections of ANP attenuated, whereas those of an antiserum against ANP intensified hyperexcitability during AW. ANP in the brain - the content of which undergoes sensitive changes in the hippocampus during AW appears to interact primarily with glutamate transmission through the NMDA-receptors. This brain structure is of utmost importance for the generation of withdrawal-related hyperexcitability. It is concluded that peripheral secretion of ANP might be a diagnostics indicator, whereas ANP in the CNS might be a modulator of AW.

Alcohol Withdrawal Delirium↗
PubMed2000

The role of atrial natriuretic peptide in alcohol withdrawal: a peripheral indicator and central modulator?

Changes in fluid and electrolyte homeostasis may accompany and are likely to modify the clinical symptoms of alcohol-withdrawal reactions. It was of obvious theoretical and practical interest therefore to investigate the changes in the secretion of hormones, which regulate the fluid and electrolyte homeostasis (atrial natriuretic peptide, aldosterone and plasma renin activity) during alcohol withdrawal in chronic alcoholic patients. In a phase of severe withdrawal, there were increased plasma renin activity and aldosterone levels observed. In a phase of partial recovery, on the other hand, the elevated plasma renin activity and aldosterone levels were back to the normal range. In 60% of the patients, delirium tremens was gradually developing during the observation period. In these patients, an elevated level of atrial natriuretic peptide was observed at the time of hospital admission, i.e. days before the actual onset of delirium tremens. It is concluded that the disturbed volume homeostasis and the consequently altered plasma atrial natriuretic peptide secretion might be associated with, and therefore used as an indicator of the onset of delirium tremens. To study the role of central nervous atrial natriuretic peptide, mice were rendered tolerant to and dependent on alcohol with an alcohol-liquid diet for 14 days. Five hours after withdrawal from alcohol, withdrawal hyperexcitability symptoms were analyzed. Intracerebroventricular (i.c.v.) injection of atrial natriuretic peptide attenuated, whereas that of an antiserum against atrial natriuretic peptide intensified the severity of handling-induced convulsions. N-methyl-D-aspartate induced behavioral seizures in a dose-dependent manner, whose effect was more intensive during the alcohol-withdrawal period than in alcohol-naive animals. I.c.v. injections of atrial natriuretic peptide dose-dependently inhibited, whereas that of antiserum against atrial natriuretic peptide potentiated the seizure-inducing effect of N-methyl-D-aspartate in alcohol-dependent mice. Although tentatively, it is concluded that peripheral secretion of atrial natriuretic peptide may be an indicator, whereas central nervous atrial natriuretic peptide a neuropeptide modulator of alcohol-withdrawal symptomatology.

Animals↗
PubMed2000

Atrial natriuretic peptide modulates N-methyl-D-aspartate-induced hyperexcitability in ethanol-dependent mice.

The role of central nervous atrial natriuretic peptide was investigated for behavioral hyperexcitability in alcohol-dependent mice. Mice were made tolerant to and dependent on ethanol with an ethanol-liquid diet for 14 days. Five hours after withdrawal from ethanol, withdrawal symptoms were analyzed by scoring handling-induced convulsions. N-methyl-D-aspartate (NMDA) induced behavioral seizures in a dose-dependent manner, an effect which was more intensive during the ethanol withdrawal period than in alcohol-naive animals. Intracerebroventricular (i.c.v.) injections of alpha-atrial natriuretic peptide (atrial natriuretic peptide) dose-dependently inhibited, whereas injection of an antiserum against atrial natriuretic peptide potentiated, the seizure-inducing effect of NMDA in ethanol-dependent mice. The main conclusion is that central nervous atrial natriuretic peptide plays a modulatory role in behavioral hyperexcitability during alcohol withdrawal.

Animals↗
PubMed1998

Oxytocin and addiction: a review.

Neuropeptides affect adaptive central nervous system processes related to opiate ethanol and cocaine addiction. Oxytocin (OXT), a neurohypophyseal neuropeptide synthesized in the brain and released at the posterior pituitary, also is released in the central nervous system (CNS). OXT acts within the CNS and has been shown to inhibit the development of tolerance to morphine, and to attenuate various symptoms of morphine withdrawal in mice. In rats, intravenous self-administration of heroin was potently decreased by OXT treatment. In relation to cocaine abuse, OXT dose-dependently decreased cocaine-induced hyperlocomotion and stereotyped grooming behavior. Following chronic cocaine treatment, the behavioral tolerance to the sniffing-inducing effect of cocaine was markedly inhibited by OXT. Behavioral sensitization to cocaine, on the other hand, was facilitated by OXT. OXT receptors in the CNS--mainly those located in limbic and basal forebrain structures--are responsible for mediating various effects of OXT in the opiate- and cocaine-addicted organism. Dopaminergic neurotransmission--primarily in basal forebrain structures--is another important biochemical mediator of the central nervous system effects of OXT. Tolerance to ethanol (e.g. hypothermia-inducing effect of ethanol) also was inhibited by OXT.

Alcoholism↗
PubMed1995

Oxytocin blocks the development of heroin-fentanyl cross-tolerance in mice.

The development of cross-tolerance to an analgesic effect was observed between two mu-receptor agonists, heroin and fentanyl. Repeated treatments with heroin twice a day for 4 days resulted in a decreased nociceptive effect to fentanyl on day 5. The fentanyl dose-response line shifted to the right, and was considered to be a sign of the development of cross-tolerance. Peripheral treatment with oxytocin did not block the development of heroin-fentanyl cross-tolerance. However, intracerebroventricular administration of oxytocin blocked the development of tolerance, causing a leftward shift in the dose-response curve and supporting the assumption that oxytocin blocks the development of heroin-fentanyl cross-tolerance via CNS mechanisms.

Analgesics, Opioid↗
PubMed1994

Barrel rotation induced by central arginine8-vasopressin treatment: involvement of neurohypophyseal peptide receptors.

Two series of experiments were done to investigate the mechanism underlying arginine8-vasopressin (AVP)-induced barrel rotation in rats. In the first series, the effect of intracerebroventricular (ICV) administration of various neurohypophyseal hormone antagonists on AVP-induced barrel rotation was studied. The more vasopressin was given, the more the rats exhibited barrel rotation. ICV pretreatment with a V1 vasopressin receptor antagonist, d(CH2)5[Tyr(Me)2]AVP, prevented barrel rotation, while similar treatment with a V2-antagonist, d(CH2)5[dIle2Ile4]AVP, did not affect vasopressin-induced barrel rotation. However, Des-Gly,NH2d(CH2)5[Tyr)Me2)Thr4Orn8]-vasotocin, a specific oxytocin antagonist, potentiated the effect of AVP on barrel rotation. The second experiment was performed in rats equipped with a telemetry system to measure heart rate (HR), core temperature (CT), and gross locomotor activity. Also, in this experiment the incidence of AVP-induced barrel rotation was dose-dependent, as was the number of rats that died. Barrel rotation was accompanied by a significant decrease in CT and HR, while rats that did not develop hypothermia did not show barrel rotation. These results suggest that a V1 receptor is involved in barrel rotation. Since AVP-induced hypothermia is also mediated by a V1 receptor, it is postulated that hypothermia is a prerequisite for barrel rotation to occur. Further experiments are needed to substantiate this hypothesis.

Animals↗
PubMed1994

Role of oxytocin in the neuroadaptation to drugs of abuse.

Oxytocin (OXT), a neurohypophyseal hormone, has a wide range of behavioral effects outside its classic peripheral endocrine functions. OXT involvement in adaptive central nervous system processes has been demonstrated as an inhibitory, amnestic action on learning and memory in different paradigms. Because adaptation and learning are likely to be involved in the neural events leading to drug tolerance and dependence, the question logically arose whether OXT is able to influence the development of tolerance of and dependence on abused drugs. In this review, we summarize our results on the effects of OXT on opiate (including morphine, heroin, and the endogenous opiates beta-endorphin and enkephalin) tolerance and dependence, heroin self-administration, psychostimulant-induced behavioral changes, and behavioral tolerance and sensitization. The sites and mechanisms of action and the possible physiological role of OXT are also discussed. In the first part of this review the effects of exogenously administered OXT on both the acute and chronic behavioral effects of opiates and psychostimulants have been summarized. OXT inhibited the development of tolerance to morphine, heroin, beta-endorphin, and enkephalin, OXT also inhibited the development of cross-tolerance between the predominantly mu-agonist heroin and the predominantly delta-agonist enkephalin in mice. Naloxone-precipitated morphine withdrawal syndrome was also attenuated by OXT. Heroin self-administration was decreased by OXT administration in heroin-tolerant rats. OXT inhibited cocaine-induced exploratory activity, locomotor hyperactivity, and stereotyped behavior in rats and in mice. Behavioral tolerance to cocaine was also attenuated by OXT. On the contrary, OXT stimulated the development of behavioral sensitization to cocaine. OXT did not alter the stereotyped behavior induced by amphetamine. In the second series of experiments, the sites of action of OXT on drug-related behavior were investigated. Intracerebro-ventricular (ICV) and intracerebral (IC) administration of an OXT-receptor antagonist inhibited the effects of peripherally administered OXT on morphine tolerance, heroin self-administration, and cocaine-induced sniffing behavior. This suggests the central, intracerebral location of OXT target sites. Local IC microinjection of OXT in physiological doses into the posterior olfactory nucleus, tuberculum olfactorium, nucleus accumbens, central amygdaloid nucleus, and the hippocampus inhibited the development of tolerance to and dependence on morphine as well as cocaine-induced sniffing behavior and tolerance to cocaine. The physiological role of endogenous OXT in acute morphine tolerance has also been demonstrated, since OXT antiserum (ICV) and OXT-receptor antagonist (injected into the basal forebrain structures) potentiated the development of morphine tolerance. Finally, we investigated the possible mechanisms of action of OXT on drug related behavior. Both morphine tolerance and dependence, and cocaine administration, increased dopamine utilization in the mesencephalon and in the nucleus accumbens, respectively. OXT treatment decreased the alpha-methylparatyrosine-induced dopamine utilization in the mesencephalon and in the nucleus accumbens-septal complex. Chronic OXT treatment decreased the number of apparent binding sites of dopamine in the basal forebrain area. It also inhibited a cocaine-induced increase in dopamine utilization in the nucleus accumbens, but not in the striatum. In light of this information, it appears that OXT inhibits the development of opiate tolerance, dependence, and self-administration as well as the acute behavioral actions of and chronic tolerance to cocaine. This suggests the possible role of this neuropeptide in the regulation of drug abuse. Therefore, OXT may act as a neuromodulator on dopaminergic neurotransmission in limbic-basal forebrain structures to regulate adaptive CNS processes leading to drug addiction.

Animals↗
PubMed1993

Alpha-atrial natriuretic peptide attenuates ethanol withdrawal symptoms.

Mice were rendered tolerant to and dependent on ethanol with an ethanol-liquid diet for 14 days. Five hours after withdrawal from ethanol, withdrawal symptoms were analyzed by scoring handling-induced convulsions. Intracerebroventricular (i.c.v.) injection of alpha-atrial natriuretic peptide (alpha-ANP) attenuated, whereas that of an antiserum against alpha-ANP (anti-ANP) intensified the severity of handling-induced convulsions.

Animals↗
PubMed1992

Oxytocin modulates behavioural adaptation to repeated treatment with cocaine in rats.

Behavioural adaptation to and the effects of the neurohypophyseal peptide, oxytocin, on repeated treatment with cocaine were investigated in rats. The content of immunoreactive oxytocin in the plasma, hypothalamus and different limbic structures in the brain were also studied after treatment with cocaine, identical to that used in the behavioural experiment. Repeated administration of cocaine (7.5 mg/kg, s.c.) produced a behavioural tolerance to the stereotyped sniffing-inducing effect of the challenge doses (1.875, 3.75 and 7.5 mg/kg, s.c.) of cocaine on the fifth day, which was demonstrated by parallel shifting of the dose-response and time-effect curves of the test doses of cocaine. The development of tolerance was inhibited by pretreatment with oxytocin (0.05 micrograms, (s.c.), administered before each daily injection of cocaine. A smaller dose of oxytocin (0.005 micrograms, s.c.) had no effect in this model. A decreased amount of immunoreactive oxytocin was detected in the plasma, in the hypothalamus and in the hippocampus, after repeated treatment with cocaine. Replacement of oxytocin by local injection (100 pg) into the ventral hippocampus, before each daily administration of cocaine, prevented the development of tolerance to cocaine. These results suggest that endogenous oxytocin, localized in limbic-forebrain areas, may have an important regulatory role in the development of behavioural changes induced by the repeated administration of cocaine.

Analysis of Variance↗
PubMed1992

Opposite actions of oxytocin and vasopressin in the development of cocaine-induced behavioral sensitization in mice.

Subchronic administration of cocaine induces behavioral sensitization (increasing hypermotility) to a challenge dose of the drug administered 72 h after the cessation of treatment. The effects of repeated administration of the neurohypophyseal hormones oxytocin (OXT) and arginine8-vasopressin (AVP) on the development of behavioral sensitization induced by subchronic treatment with cocaine were investigated in mice. Repeated treatment of OXT and AVP did not modify the locomotor stimulatory effect of the challenge dose of cocaine in cocaine-naive control animals. OXT in a dose of 0.5 microgram (sc) augmented the cocaine-induced behavioral sensitization. In contrast, AVP (0.005-0.5 microgram/mouse, sc) dose dependently attenuated the development of sensitization to the hypermotility-inducing effect of cocaine. The results suggest that the behavioral sensitization induced by cocaine can be modulated in opposite directions by neurohypophyseal hormones.

Animals↗
PubMed1992

Oxytocin blocks the development of heroin-enkephalin cross-tolerance in mice.

The development of cross-tolerance to an analgesic effect has been observed between a mu-receptor agonist, heroin, and a delta-receptor agonist, Met2-Pro5-enkephalinamide. Repeated treatments with heroin twice a day for 4 days resulted in a decreased nociceptive effect to enkephalin on day 5. The enkephalin dose-response line was shifted to the right, considered a sign of the development of cross-tolerance. Peripheral treatment with oxytocin blocked the development of heroin-enkephalin cross-tolerance. A similar effect was observed after intracerebroventricular administration of oxytocin, supporting our assumption that oxytocin blocks the development of heroin-enkephalin cross-tolerance via CNS mechanisms.

Analgesics↗
PubMed1992

Effects of cocaine on the contents of neurohypophyseal hormones in the plasma and in different brain structures in rats.

The effects of acute and chronic cocaine treatments on the levels of the neurohypophyseal hormones oxytocin (OXT) and vasopressin (AVP) in the plasma and in different brain structures in rats were measured by radioimmunoassay (RIA). Acute cocaine treatment had no effect on the level of OXT in the plasma or in the amygdala, but increased OXT contents were measured in the hypothalamus and in the hippocampus. The OXT levels in the basal forebrain structures (including the septum and the nucleus accumbens) were decreased by a single dose of cocaine. The acute injection of cocaine increased the level of AVP in the plasma, and decreased contents of OXT were measured in the amygdala and in the basal forebrain. Repeated treatment with cocaine decreased the level of OXT in the plasma, hypothalamus and hippocampus. The AVP contents were decreased in all of the brain structures investigated, but no change was caused in the plasma level of AVP by repeated injections of cocaine. These results demonstrate complex, region-specific interactions between cocaine and the neurohypophyseal hormones in the brain and in the periphery underlying the alteration in behavioral and autonomic functions caused by acute and chronic cocaine exposure.

Amygdala↗