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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have tested several compounds interfering with the brain monoamine (noradrenaline, dopamine, serotonin) and acetylcholine systems for their effects on limbic seizures produced by systemically (s.c.) injected kainic acid as well as on neurochemical changes in amygdala/pyriform cortex resulting from the kainic acid treatment. The characteristic neurochemical changes induced by s.c. kainic acid were a decrease in noradrenaline and an increase in 5-hydroxyindoleacetic acid in the acute (3 h after kainic acid injection) suggesting strongly increased neurotransmitter turnover in noradrenergic and serotonergic neurons. This was followed by a reduction of glutamic acid decarboxylase and choline acetyltransferase activities during the chronic phase (3 days) of the kainic acid action, indicating destruction of GABAergic and cholinergic neurons. The compounds tested in this model of limbic epilepsy included 1-propranolol, prazosin, clonidine, yohimbine, metergoline, atropine and haloperidol. Among these compounds the alpha 2-adrenergic agonist clonidine (0.1 mg/kg, i.p.) exhibited a powerful protective action on kainic acid-induced limbic seizures as well as on the neurochemical changes in the amygdala and pyriform cortex. In addition, the adrenoceptor antagonists prazosin (alpha 1) and propranolol (beta) as well as the dopamine receptor antagonist haloperidol had significant but less potent - protective actions upon kainic acid-induced seizures and subsequent neurochemical changes. On the other hand, yohimbine (alpha 2-antagonist) and metergoline (serotonin-antagonist) potentiated the limbic seizure syndrome and no effect was found with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha 2-adrenoceptors modulate kainic acid-induced limbic seizures. 299 67

Platelet alpha 2-and lymphocyte beta 2-adrenoceptor densities, plasma noradrenaline and serum cortisol were measured before, during and one week after a course of EEG-monitored electroconvulsive therapy, in nine depressed patients. A 50% fall in Hamilton Depression Rating scores occurred after a fairly consistent total seizure time, regardless of the amount of ECT given. Platelet alpha 2-adrenoceptor densities showed a statistically significant fall after three ECTs, but were unchanged after the full course of ECT and were independent of clinical change. Lymphocyte beta 2-adrenoceptor densities were unaltered. Plasma noradrenaline concentrations were initially high, and fell with ECT in a manner paralleling clinical recovery. Plasma noradrenaline may be a more useful index of central changes during antidepressant treatment than peripheral blood cell receptor densities.
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PMID:Adrenergic receptors in depression. Effects of electroconvulsive therapy. 299 28

The effects of administration to rats of repeated electroconvulsive shock (ECS), clenbuterol and desipramine (DMI) on beta-adrenoceptor number in cortex, and noradrenaline (NA) and dopamine (DA) turnover in whole brain has been investigated by examining the rate of decline of NA concentration (kNA) following injection of alpha-methyl-p-tyrosine. A single injection of clenbuterol (5 mg/kg) raised brain NA content and decreased the rate constant (kNA), leaving the turnover rate unaltered. Acute DMI injection decreased kNA and turnover rate, while a single ECS did not change NA metabolic rate. Repeated treatment with either ECS (5 seizures over 10 days), clenbuterol (5 mg/kg for 14 days) or DMI (5 mg/kg twice daily for 14 days) decreased beta-adrenoceptor density in cortex. No change in NA content, rate constant or turnover rate was observed after repeated ECS or clenbuterol administration. Ninety min after the last dose of DMI brain NA content was significantly decreased but kNA was unchanged compared with control animals, possibly because of the presence of subsensitive presynaptic alpha 2-adrenoceptors. At 18 hours after the last dose brain NA content was still lower than control animals but kNA was enhanced. This presumably a "withdrawal" effect, the uptake inhibitory effect of the drug now being decreased. The treatments had little effect on DA turnover apart from DMI decreasing synthesis rate. Clearly there is no obvious relationship between the ability of antidepressant treatments to alter NA turnover and decrease beta-adrenoceptor number.
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PMID:Studies on rat brain catecholamine synthesis and beta-adrenoceptor number following administration of electroconvulsive shock, desipramine and clenbuterol. 301 85

Wistar rats of a strain displaying spontaneous petit mal-like seizures and spike-wave EEG discharged (SWD) were injected i.p. with drugs affecting noradrenergic neurotransmission. The EEG and behavior were recorded. Drugs which decrease alpha-noradrenergic neurotransmission, prazosin (alpha 1-antagonist) and clonidine (alpha 2-agonist), increased SWD and were sedative in a dose-dependent manner. Drugs which increase alpha-noradrenergic neurotransmission, ST 587, cirazoline (alpha 1-agonists) and yohimbine (alpha 2-antagonist), reduced SWD and the latter two caused agitation. Drugs which interact with beta-noradrenergic transmission (salbutamol, isoprenaline and propranolol), monoamine oxidase inhibitors (nialamide and iproniazid), and a noradrenaline reuptake inhibitor (desipramine), did not affect SWD. These findings suggest that noradrenaline participates in the control of petit mal-like seizures in the rat, as in other types of seizures and other animal models.
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PMID:Effects of drugs affecting noradrenergic neurotransmission in rats with spontaneous petit mal-like seizures. 303 36

The electroencephalographic (EEG) response of 6-hydroxydopamine (6-OHDA)-treated and control rats to gamma-butyrolactone (GBL) the prodrug of gamma-hydroxybutyrate (GHB), was determined. Neonatal treatment with 6-OHDA produced a significant reduction of noradrenaline in cortex and hippocampus while sparing noradrenaline in the hypothalamus. Brain dopamine was unaffected. The electrographic seizure produced by GBL was significantly prolonged and more severe in the 6-OHDA-treated animals. That portion of the hypersynchronous seizure induced by GBL which is pharmacologically sensitive to antipetit mal anticonvulsants, Stage 1, was however shortened in the 6-OHDA-treated animals. Reduction of forebrain noradrenaline seems to have a complex effect on GBL-induced seizure in that it results in a reduction of hypersynchronous EEG activity but in a prolongation of the more severe EEG changes of burst suppression normally seen with higher doses of GBL.
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PMID:Noradrenergic mechanisms in gamma-hydroxybutyrate-induced seizure activity. 310 25

The effect of mannitol treatment on the behavioural, morphological and neurochemical brain damage induced after subcutaneously applied kainic acid (10 mg/kg) was studied in the rat. Mannitol at a dose of 1.5 g/kg was injected intravenously 10 min, 1.5 h and 3 h respectively after kainic acid administration. A protective effect of mannitol was observed only when mannitol was given 1.5 h after kainic acid application, i.e. within the early phase of kainic acid-induced brain oedema development. At this time period, mannitol prevented the development of kainic acid-induced seizures as well as irreversible brain lesions and neurochemical changes, the latter being reduction of noradrenaline levels in amygdala/pyriform cortex measured 3 h, and reduction of glutamate decarboxylase and choline acetyltransferase activities measured 3 days after kainic acid treatment. Similarly loss of glutamate decarboxylase activity in dorsal hippocampus induced by kainic acid was prevented by mannitol treatment. It is concluded that by washing out brain oedema, mannitol treatment may prevent propagation of seizures and brain damage in the kainic acid model of epilepsy.
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PMID:Effect of mannitol treatment on brain neurotransmitter markers in kainic acid-induced epilepsy. 311 66

The characteristics and pattern of the acceleration of kindling produced by 6-hydroxydopamine-induced depletion of noradrenaline (NA) were investigated in adult rats receiving electrical stimulation of the amygdala once daily. NA-depleted rats developed generalized seizures very rapidly by spending significantly less time than controls in the early stages of nonconvulsive or partial seizures, and they required significantly less cumulative total time in afterdischarge than controls to develop generalized seizures. The results suggest that attempts to identify noradrenergic correlates of kindling should be directed to the early stages of seizure development.
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PMID:Characteristics of accelerated kindling after depletion of noradrenaline in adult rats. 314 71

The petit-mal seizures of the "tottering" mutant mouse (tg) have been attributed to an exaggerated noradrenergic projection from locus coeruleus to the telencephalon (Noebels 1984). In order to investigate the possible epileptogenic mechanisms involved, we have compared hippocampal slices from epileptic (tg/tg) and phenotypically healthy (tg/+) mice. Resting potentials, action potentials and afterpotentials, membrane impedances and time constants were not significantly different in 11 neurons from each group. Bath application of noradrenaline, isoproterenol and histamine or a transient exposure to Mg++-free medium caused a long lasting increase in extracellularly recorded population spikes induced in CA1 by electrical stimulation of stratum radiatum. Isoproterenol blocked the calcium dependent afterhyperpolarization and accommodation of firing. Tetanization of afferent fibres evoked post-tetanic potentiation and long-term potentiation. All these results are qualitatively similar to those previously described in rats and guinea pigs and have revealed no significant difference between tg/tg and tg/+ mice.
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PMID:Membrane properties, response to amines and to tetanic stimulation of hippocampal neurons in the genetically epileptic mutant mouse tottering. 316 95

Abnormalities in noradrenaline-mediated neurotransmission have been advocated as a basis of the age-related susceptibility of DBA/2J mice to generalised convulsions induced by auditory stimulation. We have measured the kinetics of synaptosomal high-affinity noradrenaline uptake in 5 brain regions of DBA/2J mice at ages before, during and after their maximal susceptibility to audiogenic seizures, and age-matched C57 BL/6 mice, a strain resistant to audiogenic seizures at all ages. No differences were found between the two strains of mice in any of the brain regions studied. Abnormalities of high-affinity noradrenaline uptake do not contribute to audiogenic seizure susceptibility of DBA/2J mice.
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PMID:Synaptosomal high-affinity noradrenaline uptake does not differ between mice susceptible (DBA/2J) and resistant (C57 BL/6) to audiogenic seizures. 350 89

Brain catecholamines (noradrenaline and dopamine) seem to suppress certain forms of epileptic activity. In this paper we report the catecholaminergic influences on hippocampal paroxysmal activity in rats induced through hippocampal electrical stimulation via stereotaxic electrode placements. The experiments included: (1) systemic injections of clonidine (0.10 mg/kg); phenoxybenzamine (10 mg/kg); propranolol (10 mg/kg); apomorphine (1 mg/kg) and haloperidol (1 mg/kg) and (2) electrolytic lesions of the locus coeruleus ipsilateral to the stimulated hippocampus. The clonidine group showed a great reduction, while animals which received phenoxybenzamine showed a significant increase in the electrographic seizure activity. Propranolol produced only a transient reduction of epileptic activity. We did not observe any significant change in the epileptic discharges following apomorphine and haloperidol injections. Electrolytic lesions of the locus coeruleus induced a clear enhancement of the epileptiform activity. The results presented here support the view that noradrenergic, but not dopaminergic systems, may exert a tonic inhibitor effect on hippocampal epileptic activity.
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PMID:Catecholaminergic influences on induced hippocampal paroxysmal activity in rats. 357 4


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