Biomedical subjects

M Hajós

Publications and source records attributed to M Hajós.

At least 37 records · Page 2Linked to original sources

PubMed1992

Differential actions of acetylcholinesterase on the soma and dendrites of dopaminergic substantia nigra neurons in vitro.

In the substantia nigra, acetylcholinesterase (AChE) has non-cholinergic action on dopaminergic neurons. The subset of neurons particularly sensitive to AChE are characterized by functionally active apical dendrites extending into the pars reticulata and generating a powerful calcium conductance. This study thus attempted to establish directly the importance of these dendrites regarding the action of AChE. Segregation of the pars compacta from the pars reticulata did not affect the AChE-induced hyperpolarization on this sub-set of dopaminergic neurons. However, the ionic basis of the hyperpolarization was related to the integrity of the neurons: AChE caused an opening of potassium channels in intact cells. On the other hand when the pars reticulata containing apical dendrites was removed, an action of AChE involving the closure of calcium/sodium channels was revealed. The results demonstrate that the net effect of AChE need not be related to any particular segment of the dopaminergic neurons, whereas the nature of the mechanism underlying that effect depends on the presence, or otherwise, of the apical dendrites.

Acetylcholinesterase↗

PubMed1992

Ethanol attenuates the response of locus coeruleus neurons to excitatory amino acid agonists in vivo.

Recent in vitro electrophysiological studies have revealed that ethanol specifically reduces N-methyl-D-aspartate (NMDA)-activated ion currents, e.g. in hippocampal slices. In the present study, utilizing extracellular recording techniques, the effect of ethanol on excitatory amino acid induced excitability of rat locus coeruleus noradrenergic neurons was investigated in vivo. Administration of ethanol (2 g/kg, i.p.) significantly inhibited the excitation of the locus coeruleus neurons as produced by microiontophoretic application of glutamate, NMDA or quisqualate, but not that of kainate. In contrast, the locus coeruleus response to similarly applied acetylcholine was unaffected by the ethanol treatment. Although ethanol did not alter the basal firing rate of locus coeruleus neurons, the drug significantly changed the firing pattern of the neurons into a more regularized rhythm. It is proposed that the presently observed attenuation of glutamate excitation of locus coeruleus by ethanol may constitute part of the underlaying mechanism for ethanol intoxication in man.

Acetylcholine↗

PubMed1992

Alcohol withdrawal reaction as a result of adaptive changes of excitatory amino acid receptors.

Recent electrophysiological and biochemical studies suggest that ethanol interferes with excitatory amino acid (EAA) neurotransmission. Here, we present electrophysiological evidence that, following cessation of a chronic ethanol treatment, noradrenergic locus coeruleus (LC) neurons display hyperactivity at the same time as a specifically enhanced sensitivity to microiontophoretically applied NMDA or quisqualate. Furthermore, after chronic ethanol treatment, but not before, the NMDA receptor antagonist MK 801 (0.3-2.4 mg/kg, i.v.) dose-dependently inhibited the firing of the LC neurons. Our data indicate that an up-regulation of EAA receptors located on LC neurons accounts for the changes in LC firing in ethanol-treated rats. We propose that activation of the LC contributes to the clinical signs of the ethanol abstinence reaction and that EAA antagonists may be beneficial therapeutically for its treatment.

Animals↗

PubMed1991

Possible morphological correlates of capsaicin desensitization.

The changes in the fine structure of axonal profiles of the guinea-pig ureter were examined after exposure to capsaicin in vitro. In the ureters exposed to capsaicin (1-10 microM), about 60%, of all axonal profiles exhibited conspicuous ultrastructural impairment. It is suggested that these alterations might interfere with the release of peptides from these particular nerve endings and therefore contribute significantly to the mechanisms of capsaicin desensitization.

Animals↗

PubMed1991

Ruthenium red inhibits tail skin vasodilatation evoked by intracerebroventricular injection of capsaicin in the rat.

The effect of Ruthenium red on the tail skin vasodilatation evoked by an intracerebroventricular injection of capsaicin was studied in the anesthetized rat. Injection of capsaicin into the lateral ventricle resulted in a marked elevation of the tail skin temperature, indicative of peripheral vasodilatation. Ruthenium red, given by intracerebroventricular injection, significantly inhibited this response, which is known to be mediated by central warmth-sensitive neuronal structures. The findings suggest that the sensitivity to Ruthenium red, reportedly characteristic of the capsaicin-sensitive neurons in the peripheral nervous system, is also a trait of the capsaicin-sensitive nerve cells in the central nervous system. This is the first evidence indicating that similar molecular mechanisms, presumably involving changes in cellular calcium metabolism, contribute to the capsaicin-induced activation of neurons in both the peripheral and central nervous systems.

Animals↗

PubMed1990

A role of excitatory amino acids in the activation of locus coeruleus neurons following cutaneous thermal stimuli.

Previous electrophysiological experiments have shown that brain noradrenaline neurons in the locus ceruleus are activated by thermal cutaneous stimuli. In the present study a putative involvement of excitatory amino acids (EAA) in cutaneous LC activation was analyzed. Intraventricular administration of kynurenic acid (1 mumol), a broad spectrum EAA antagonist, or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.1 mumol) as well as subcutaneous administration of the specific NMDA antagonist MK 801 (2 mg/kg) almost totally abolished the response of LC neurons to both non-noxious and noxious cutaneous sensory stimuli. We propose that the activation of LC neurons following thermal cutaneous stimuli is mediated via release of EAA from nerve terminals emanating from nucleus paragigantocellularis (PGi).

Afferent Pathways↗

PubMed1990

Kynurenic acid blocks chemogenic nociception.

Previous studies have suggested a role of excitatory amino acids (EAA) in nociception. In the present study the effects of two antagonists of EAA-receptors on capsaicin-induced eye wipings were investigated. Intracisternally administered kynurenic acid, in contrast to intravenously administered MK-801, was found to effectively block the induced eye wipings. It is proposed that EAA, by activating non-NMDA receptors, are involved in the transmission of chemogenic nociception.

Animals↗

PubMed1988

Role of primary sensory neurons in the central effects of nicotine.

Utilizing single unit recording techniques the nicotine-induced excitation of noradrenaline (NA)-containing neurons in the locus coeruleus (LC) was analyzed. Low doses of nicotine (40-160 micrograms, IV) were found to dose-dependently increase the LC firing rate. The effect was antagonized by pretreatment with the quaternary ganglionic blockers hexamethonium (12 mg/kg, IP) and chlorisondamine (0.3 mg/kg, IV). Also, neonatal treatment with capsaicin, a procedure that is associated with a selective degeneration of primary sensory C-fibre afferents, clearly antagonized the effect of nicotine on LC neurons. The typical effect of nicotine on LC discharge was, in all essentials, mimicked by the quaternary nicotinic agonist tetramethylammonium (TMA). We here propose that the action of nicotine on central NA neurons is primarily executed peripherally via activation of primary sensory C-fibre afferents.

Animals↗

PubMed1988

Capsaicin-sensitive vasodilatatory mechanisms in the rat substantia nigra and striatum.

Thermoregulatory and neurochemical effects of capsaicin microinjection into the substantia nigra (SN) or caudatus putamen (CPu) were studied in rats. Administration of capsaicin into these brain structures induced a peripheral vasodilatation which was associated with a decrease in body temperature. Pretreatment of the rats with capsaicin either as adults or neonates abolished the thermolytic response to the drug, indicating that the effect is executed specifically upon capsaicin sensitive structures. Analyses of the levels of monoamines and their metabolites in the striatum following injection of capsaicin into the SN or CPu revealed that dopaminergic neurons are not primarily involved in this effect. This view is also supported by our findings that neurochemical lesion of unilateral nigrostriatal dopaminergic neurons did not influence the vasodilatatory response. Since the pharmacological effect of intranigral capsaicin was not abolished by unilateral axotomy (hemisection) we presume a capsaicin-sensitive, non-dopaminergic descending vasodilatatory pathway from the SN.

Action Potentials↗

PubMed1987

Spinal cord alpha 2-adrenoceptors may be located postsynaptically with respect to primary sensory neurons: destruction of primary C-afferents with neonatal capsaicin does not affect the number of [3H]clonidine binding sites in mice.

Mice were treated with 50 mg/kg capsaicin on the second day of life, which causes a permanent and selective loss of a large proportion of afferent C-fibers. Two months later the spinal cords were removed and the content of alpha 2-adrenoceptors assayed by radioligand binding with [3H]clonidine. In these tests the content of alpha 2-adrenoceptors was found to be 568 +/- 27 fmol/mg protein in the capsaicin-treated animals and it was virtually the same -596 +/- 9 fmol/mg protein - in control animals. The affinity of [3H]clonidine for the alpha 2-adrenoceptor was not affected by capsaicin (Kd = 3.25 +/- 0.29 nM for capsaicin and 3.23 +/- 0.32 nM for the controls). In functional tests clonidine applied s.c. induced a marked reduction in the pain sensitivity to capsaicin. The results indicate that spinal cord alpha 2-adrenoceptors are located postsynaptically with respect to the primary sensory neurons and potentially that stimulation of these receptors by alpha 2-adrenoceptor agonist mediates inhibition of nociceptive transmission.

Animals↗

PubMed1987

Injection of capsaicin into the nucleus raphe dorsalis elicits heat loss in the rat.

The acute thermoregulatory effect of microinjection of capsaicin into the nucleus raphe dorsalis (NRD) has been studied in anesthetised rats. Application of capsaicin (20 micrograms) into the NRD increased the tail skin temperature and decreased the body temperature. In animals that had previously been treated with capsaicin (50 mg/kg s.c.) the thermolytic effect of capsaicin microinjection was completely abolished. Additionally, the effects of NRD capsaicin injection on the monoamines in the preoptic region + hypothalamus (RPO-H) were studied. Levels of noradrenaline, dopamine, serotonin, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by means of liquid chromatography. Neurochemical analysis of RPO-H showed no changes in the serotonin metabolism, but an elevated DOPAC level 30 min after the injection of capsaicin into the NRD.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Dopamine autoreceptor antagonists: effects on sleep-wake activity in the rat.

The effects of the putative dopamine (DA) autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, and cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, on sleep-wake activity, EEG, and motor activity in the rat were studied. Both drugs induced a dose-dependent increase in wakefulness (W) and a reduction in non-REM sleep (NREMS). A definite tendency to a suppression of REM sleep (REMS) could also be observed. The results of spectral analysis indicated that EEG slow wave activity, a marker of sleep intensity, was particularly sensitive to the drugs. Slight differences between the two drugs were observed: (+)-AJ 76 seemed to be more efficacious than (+)-UH 232 in stimulating motor activity. (+)-UH 232 tended to suppress slow wave activity more strongly than (+)-AJ 76. It is suggested that the increase in W following administration of (+)-AJ 76 resulted predominantly from locomotor activation, while (+)-UH 232 might also act on dopaminergic mechanisms involved in the regulation of sleep.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1987

Capsaicin-induced excitation of locus coeruleus neurons.

The noradrenergic pontine nucleus locus coeruleus (LC) seems to be involved in sensory processing. In the present study, the effect of capsaicin, a drug which specifically interferes with chemosensitive primary afferents, on LC firing rate was analysed, utilizing electrophysiological techniques. In control rats, low doses of capsaicin (1-8 micrograms kg-1 i.v.) caused a marked excitation of LC units. The effect was instantaneous in onset but short-lasting and no signs of tachyphylaxis were observed. The excitation was maintained in adult rats treated as neonates with high doses of capsaicin (50 mg kg-1 s.c.) but almost totally prevented by pretreatment of adult rats with high doses of capsaicin (300 mg kg-1 s.c.). According to our histological data, using selective silver impregnation techniques, the LC seems not to receive innervation by sensory primary afferents. It is proposed that the capsaicin-induced excitation of LC neurons is a centrally mediated effect and might, in part, be involved in the analgetic effect induced by the drug.

Animals↗

PubMed1987

Differences in the mechanisms of the thermoregulatory impairment induced by capsaicin in newborn and adult rats.

The function of heat defence was compared in rats pretreated as adults (A-rats) and neonates (N-rats) with capsaicin. The thermoregulatory impairment as tested by whole body heating was similar in A-rats and N-rats. The thermosensitivity and chemosensitivity of the preoptic region (RPO) seemed to be normal in N-rats. A deficiency of RPO mechanisms could be demonstrated in A-rats. It is suggested that the preoptic effects of capsaicin have but a minor significance for the thermoregulatory impairment. It seems that the main cause of decreased heat tolerance is a reduction of peripheral warm sensation due to degeneration of unmyelinated C-fibre primary neurons in both A-rats and N-rats. The results do not support the primary importance of preoptic warm sensation in physiological thermoregulation.

Animals↗

PubMed1986

Reduced responsiveness of locus coeruleus neurons to cutaneous thermal stimuli in capsaicin-treated rats.

Recent electrophysiological experiments have shown that brain norepinephrine (NE) neurons in the locus coeruleus (LC) are activated by cutaneous thermal stimuli of both non-noxious and noxious character. In the present study the LC neuronal response to thermal stimuli was used to evaluate cutaneous thermal sensitivity in capsaicin-treated rats, a treatment that is described to cause impaired thermoregulation. Capsaicin treatment, of neonates as well as of adult rats, caused a reduced responsiveness of brain LC neurons to thermal stimuli. The results suggest that a reduction in peripheral thermal afferent transmission may be one mechanism underlying the capsaicin-induced thermoregulatory dysfunction.

Age Factors↗

PubMed1986

Emotional hyperthermia in spontaneously hypertensive rats.

Basal body temperature of spontaneously hypertensive rats (SHR) was found to be significantly elevated compared to normotensive Wistar Kyoto rats (WKR). The hypothermic response to low doses of the alpha 2-receptor agonist clonidine was significantly smaller in SHR compared to WKR. In contrast, the thermoregulatory response of SHR to a non-noxious stressor was heightened. We propose that the elevated basal temperature observed in SHR is not due to an impaired thermolysis but the result of a noradrenaline-mediated hyperreactivity to environmental stress, e.g. handling of the animals during the temperature measurement procedure.

Animals↗

PubMed1986

Effects of capsaicin on central monoaminergic mechanisms in the rat.

The acute and chronic effects of capsaicin (s.c.) on the monoamines in the preoptic region + hypothalamus (RPO-H), spinal cord, substantia nigra and striatum were studied. Levels of DOPA, DA, DOPAC, HVA, 3-MT, NA, Trp, 5-HTP, 5-HT and 5-HIAA were determined by means of liquid chromatography (HPLC-EC). In response to acute capsaicin treatment, the levels of DA, DOPAC and DA synthesis rate (DOPA formation) were increased in a dose-dependent manner in the RPO-H and spinal cord. The disappearance rate of NA was accelerated in both regions. In substantia nigra, increased DOPAC levels were found whereas the levels of 3-MT were decreased in striatum after acute capsaicin treatment. Only minor changes on the levels of 5-HT and 5-HIAA in the regions studied were noted. Neonatal or adult capsaicin treatment failed to affect the levels of NA, DA and 5-HT (measured two months or five weeks after injection, respectively) in the regions studied. A capsaicin injection to rats pretreated with the drug as adults did not affect either the monoamines in the RPO-H and spinal cord or the body temperature. In contrast, in rats pretreated with capsaicin as neonates, a second injection of the drug to adult animals elicited hypothermia and changes in monoamines similar to those observed in naive animals.

Animals↗

PubMed1986

Structure-activity relationship in the effects of delta-sleep-inducing peptide (DSIP) on rat sleep.

DSIP and its analogues, [D-Trp1]-DSIP, [D-Tyr1]-DSIP, and [D-Trp1]-DSIP1-6, were injected ICV (7 nmol/kg) into rats at dark onset, and the sleep-wake activity was recorded during the 12-hr dark period and the subsequent 12-hr light period. The effects were evaluated with respect to baseline records obtained after artificial CSF injections. DSIP did not increase sleep, whereas both [D-Trp1]-DSIP and [D-Tyr1]-DSIP promoted sleep in the first part of the night. [D-Trp1]-DSIP1-6 had a prompt arousing effect. It is suggested that the sleep-promoting analogues act by facilitating slight endogenous sleep tendencies at some time after dark onset, while DSIP is degraded quickly and is therefore not effective. The increase of W after [D-Trp1]-DSIP1-6 may indicate that DSIP contains a fragment with an arousing effect. The results corroborate the notion that the active DSIP molecule has a pseudo-cyclic structure.

Animals↗