Strong olfactory stimulation reduces seizure susceptibility in amygdala-kindled rats.

Seizures in human temporal lobe epilepsy are characterized by paroxysmal activity in the limbic system. The primary olfactory or piriform cortex is a central part of the limbic system. Since a relationship between olfactory sensation and limbic seizures has been described, we were interested in the effect of strong olfactory stimulation on the seizure susceptibility of amygdala-kindled rats, a model of human temporal lobe epilepsy.

Paradoxical aggravation of paroxysmal dystonia during chronic treatment with phenobarbital in a genetic rodent model.

Recent studies in mutant hamsters (dt(sz)), an animal model of primary paroxysmal dystonia, indicated that altered function of the gamma-aminobutyric acid (GABA)ergic system plays a critical role in the pathogenesis of dystonia. In the present study, dt(sz) hamsters were chronically treated with phenobarbital, which has been found to exert antidystonic effects in mutant hamsters after acute administration. In untreated dt(sz) hamsters, the severity of dystonia follows an age-dependent time course with a maximum between the 30th and 40th day of life, followed by a continuous decline of severity until complete remission occurs at the age of about 70 days.

Repeated acute testing of anticonvulsant drugs in amygdala kindled rats: increase in anticonvulsant but decrease in adverse effect potential.

Purpose: Because preparation of kindled rats is laborious, time-consuming, and expensive, such animals are often used for several experiments in the evaluation of anticonvulsant drugs (AEDs). Furthermore, for comparison with data on new drugs, often "historical" data on standard drugs obtained in previous experiments in other groups of kindled rats are used. Without knowing how factors such as repeated drug testing or seasonal variation in drug responses affect drug potencies in the kindling model, false conclusions and predictions might be drawn from such comparisons.

Evidence for striatal dopaminergic overactivity in paroxysmal dystonia indicated by microinjections in a genetic rodent model.

Mutant dystonic hamsters (dt(sz)), a model of primary paroxysmal dystonia, display attacks of generalized dystonia in response to mild stress in an age-dependent manner. Recent studies in dystonic hamsters have revealed decreased densities of dopamine D(1) and D(2) in the dorsal striatum. This finding has been interpreted as a down-regulation in response to enhanced dopamine release because systemic treatments with neuroleptics reduced the severity of dystonia while levodopa exerted prodystonic effects.

A microdialysis study of striatal dopamine release in the circling rat, a genetic animal model with spontaneous lateralized rotational behavior.

The circling rat is an autosomal recessive mutant (homozygous ci2/ci2) that displays lateralized circling behavior, locomotor hyperactivity, hyperexcitability, ataxia, and stereotypic head-movement. These abnormal behaviors are induced or intensified by stress. Heterozygous (ci2/+) littermates display normal spontaneous behaviors.

Anticonvulsant efficacy of gabapentin and levetiracetam in phenytoin-resistant kindled rats.

We evaluated the anticonvulsant efficacy of the new antiepileptic drugs (AEDs) gabapentin and levetiracetam in amygdala kindled rats that had been preselected with respect to their response to phenytoin. Anticonvulsant response was tested by determining the afterdischarge threshold (ADT), i.e.

Kindling alters the anticonvulsant efficacy of phenytoin in Wistar rats.

We have previously shown that subgroups can be selected from large groups of amygdala kindled Wistar rats which either respond consistently or do not respond to the anticonvulsant effect of phenytoin. Phenytoin nonresponders were proposed as a model for pharmaco-resistant temporal lobe epilepsy. In the present study we examined whether the differences of individual rats in response to phenytoin are already present before kindling or are a consequence of kindling.

Anticonvulsant efficacy of topiramate in phenytoin-resistant kindled rats.

Purpose: We evaluated the anticonvulsant efficacy of topiramate (TPM), a structurally novel antiepileptic drug (AED), in amygdala kindled rats that had been preselected with respect to their response to phenytoin (PHT).

Methods: Anticonvulsant response was tested by determining the afterdischarge threshold (ADT; i.e.

Piracetam and levetiracetam, two pyrrolidone derivatives, exert antidystonic activity in a hamster model of paroxysmal dystonia.

The effects of the nootropic drug piracetam and its analogue, the antiepileptic drug levetiracetam (ucb L059) on severity of dystonic attacks were studied in a mutant hamster model of idiopathic generalized dystonia. Both drugs significantly decreased the severity of dystonia. In contrast to seizure models, in which levetiracetam is much more potent as an anticonvulsant than piracetam, the antidystonic potency of levetiracetam was only moderately higher than that of piracetam.

Development of kindling and spontaneous seizures after massed stimulation of different loci in the rat piriform cortex.

Massed electrical stimulation of the anterior piriform cortex (PC) in rats using short (5 min) interstimulus intervals has previously been reported to induce severe chronic epilepsy with spontaneous seizures and has thus proposed to represent a novel model of temporal lobe epilepsy. In the present study, we used this stimulation protocol to evaluate the frequency and severity of recurrent spontaneous seizures produced in this way. In addition to the locus in the anterior PC previously used for massed stimulation (MS), we also stimulated rats via a locus in the transition zone between anterior and posterior PC ("central PC"), which previously was found to be more sensitive to electrical stimulation than various other loci in the anterior or posterior PC.

Gabapentin-lactam, a close analogue of the anticonvulsant gabapentin, exerts convulsant activity in amygdala kindled rats.

The cyclic GABA analogue gabapentin (GBP), which recently has been marketed for treatment of epilepsy, is particularly effective against complex-partial seizures as occurring in temporal lobe epilepsy. In the present study, we compared the effects of GBP and its lactam analogue (GBP-L) in the amygdala kindling model of temporal lobe epilepsy. In fully kindled rats, GBP (50 mg/kg and 100 mg/kg i.

Load-dependence of fatigue related changes in tremor around 10 Hz.

Objectives: The aim of the study was to investigate the effects of different loads on tremor around 10 Hz during fatiguing contractions.

Methods: Eighteen healthy volunteers performed sustained isometric knee extensions at 30%, 50% and 70% maximum voluntary contraction (MVC). During the fatiguing contractions, mechanical recordings were made with a high-resolution force sensor.

The role of technical, biological, and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. VII. Seasonal influences on anticonvulsant drug actions in mouse models of generalized seizures.

Seasonal or circannual rhythms have been reported in various physiologic, biochemical, pharmacological, and toxicological studies in mice and rats despite laboratory conditions with standardized and controlled light cycle, temperature, humidity, and food. This may either be explained by the existence of innate, free-running circannual rhythms or by the existence of seasonally varying environmental factors ('zeitgeber') which are detected by the animals despite controlled laboratory conditions. In the present study, it was evaluated whether circannual rhythms affect the anticonvulsant activity of phenobarbital, carbamazepine, or valproate in two mouse models of generalized seizures, i.

[Hereditary motor-sensory neuropathies (Charcot-Marie-Tooth syndrome) and related neuropathies. Current classification and genotype-phenotype correlation].

Charcot-Marie-Tooth (CMT) disease is the most common inherited disorder of the peripheral nervous system with an incidence of 40:100,000. Clinically, it is characterized by distal muscle weakness and wasting, primarily of the legs and later of the arms, foot deformity, diminished or absent tendon reflexes, and mild-to-moderate sensory loss. Molecular genetic studies over the past 2 decades have revealed the genetic heterogeneity of this disorder and the identification of different genes or gene loci, respectively.

Expression of cholecystokinin, somatostatin, thyrotropin-releasing hormone, glutamic acid decarboxylase and tyrosine hydroxylase genes in the central nervous motor systems of the genetically dystonic hamster.

In the dt(sz) mutant hamster with idiopathic generalized dystonia, functional abnormalities of several neurotransmitters have been suggested to play a role in the development of symptoms. In the present study, we have used histochemistry with (35)S-ATP labeled oligonucleotides to determine whether these abnormalities are associated with modulation in the expression of neurotransmitter genes in motor regions. We examined the expression of genes encoding cholecystokinin (CCK), somatostatin (SRIF), thyrotropin-releasing hormone (TRH), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) in the cortex and basal ganglia of dystonic hamsters and of non-dystonic control hamsters of a related inbred line and of a non-related outbred line.

Corneal kindling in mice: behavioral and pharmacological differences to conventional kindling.

Electrical kindling via unilateral implanted depth electrodes in rats is currently the most commonly used model for temporal lobe epilepsy, but the use of this model in drug screening for the identification of novel anticonvulsants is markedly hampered by the laborious and time-consuming preparation and the size of the animals. Kindling of male mice via transcorneal electrical stimulation has recently proposed as a cost-effective screening model that may improve the preclinical evaluation of efficacy and adverse effect potential of drug candidates for treatment of partial epilepsy. In the present study, corneal kindling was characterized and compared in male and female mice.

Effect of depth electrode implantation with or without subsequent kindling on GABA turnover in various rat brain regions.

Kindling is a chronic model of epilepsy characterized by a progressive increase in response to the same regularly applied electrical stimulus. The biological basis of the kindling phenomenon requires to be determined, but several studies indicate that impairment of GABAergic inhibition may be involved. In the present experiments, GABA turnover was determined in vivo by the GABA aminotransferase (GABA-T) inhibition method in 13 brain regions in three groups of rats: (1) a group which was kindled via electrical stimulation of intra-amygdala electrodes and was sacrificed 36 days after the last fully kindled seizure for neurochemical determinations; (2) a group of implanted but non-stimulated rats (sham control group) in which neurochemical measurements were done at the same time after electrode implantation as in the kindled group; and (3) a group of non-implanted, naive control rats.

Lymphocyte subset analyses in blood, spleen and lymph nodes of female Sprague-Dawley rats after short or prolonged exposure to a 50 Hz 100-microT magnetic field.

Based primarily on the results of in vitro studies, it has been suggested that power-line (50 or 60 Hz) magnetic fields (MFs) may reduce immune function, which could lower resistance to infection or cancer. This study was conducted to evaluate the influence of acute and chronic in vivo exposure to a linearly polarized 50 Hz MF on immune function in female Sprague-Dawley rats. Groups of rats were exposed continuously to the MF at a flux density of 100 microT for periods of 3 days, 14 days or 13 weeks.

In vivo extracellular electrophysiology of pallidal neurons in dystonic and nondystonic hamsters.

In the dt(sz) hamster, a model of idiopathic paroxysmal dystonia, recent findings indicated a decreased neuronal activity within the globus pallidus (GP) and an impaired gamma aminobutyric acid (GABA)ergic function when compared to nondystonic controls. Therefore, in the present study, extracellular single-unit recordings combined with systemical application of a subconvulsant prodystonic dose of pentylenetetrazole (PTZ) were used to compare the electrophysiological properties of GP neurons in anesthetized dt(sz) hamsters and nondystonic controls. The spontaneous discharge rate of GP neurons was not decreased but a trend towards a wide-ranged distribution was found in mutants compared to controls.

5'-Nucleotidase activity of mossy fibers in the dentate gyrus of normal and epileptic rats.

Sprouting of mossy fibers in the hippocampus of rats that underwent limbic epileptogenesis by amygdala kindling or kainate injection was studied at the light microscopic and ultrastructural levels by cytochemical demonstration of the enzyme 5'-nucleotidase. This adenosine-producing ectoenzyme has previously been shown to characterize malleable terminals during brain development and lesion-induced synaptogenesis, but to be otherwise associated with glial membranes. At the light microscopic level, kainate-treated but not control or kindled rats showed 5'-nucleotidase activity in the CA3 region and in the inner molecular layer of the dentate gyrus.

Alterations in ornithine decarboxylase activity in the rat mammary gland after different periods of 50 Hz magnetic field exposure.

In a series of experiments with the chemical carcinogen DMBA (7, 12-dimethyl[a]anthracene), we recently found that exposure of female Sprague-Dawley rats in 50 Hz magnetic fields (MF) in the microtesla range significantly facilitates the development and growth of mammary tumors. One possible explanation for this finding would be enhanced proliferation of breast epithelial stem cells by MF exposure, thereby increasing the sensitivity of these cells to chemical carcinogens. In line with this possibility, we previously determined that 50 Hz, 50 microT MF exposure induces increases in ornithine decarboxylase (ODC), i.

Exposure of Sprague-Dawley rats to a 50-Hertz, 100-microTesla magnetic field for 27 weeks facilitates mammary tumorigenesis in the 7,12-dimethylbenz[a]-anthracene model of breast cancer.

We have shown previously (W. Löscher et al., Cancer Lett.

Effects of the NMDA receptor antagonist D-CPPene on extracellular levels of dopamine and dopamine and serotonin metabolites in striatum of kindled and non-kindled rats.

Electrical kindling in rats has previously been shown to cause a hypersensitivity to amphetamine-like behavioral effects of competitive NMDA receptor antagonists such as D,L-(E)-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849), D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 40116), or 3-(2-carboxypiperazine-4-yl)propenyl-1-phosphonate (SDZ EAA 494; D-CPPene). From this observation, it was concluded that kindling-induced epileptogenesis enhances the potential of competitive NMDA receptor antagonists to induce such unwanted adverse effects, predicting that such drugs may induce more severe side effects in epileptic patients than in healthy volunteers, which was confirmed in clinical trials. In the present study, we thought to examine the biochemical basis for the enhanced susceptibility of kindled rats to amphetamine-like behavioral effects of NMDA receptor antagonists by measuring extracellular levels of dopamine, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin (5-hydroxytryptamine, 5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of awake, behaving rats, using in vivo microdialysis.

Subconvulsive dose of pentylenetetrazole increases the firing rate of substantia nigra pars reticulata neurons in dystonic but not in nondystonic hamsters.

Dystonic attacks, including twisting movements, can be initiated by mild stress in mutant (gene symbol dt(sz)) Syrian golden hamsters, an animal model of idiopathic paroxysmal dystonia. Previous studies suggested that dysfunctions in basal ganglia, which are not restricted to periods of attacks, are involved in the dystonic syndrome in mutant hamsters. Therefore, in the present study in anesthetized animals, we examined whether the spontaneous firing rate of extracellularly recorded neurons of the substantia nigra pars reticulata (SNr) differs between dt(sz) and age-matched nondystonic control hamsters.

Exposure of rats to a 50-Hz, 100 muTesla magnetic field does not affect the ex vivo production of interleukins by activated T or B lymphocytes.

Two separate, independent experiments were conducted to evaluate the effects of exposure of rats to a 50-Hz linearly polarized, 100 microT magnetic field (MF) on the ex vivo production of interleukins (ILs) by mitogen-stimulated splenic lymphocytes. IL-1 and IL-2 were determined by proliferation assays, using IL-dependent murine T cell lines. In the first experiment, female Sprague-Dawley rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA] at a dose of 20 mg per rat (four weekly gavage doses of 5 mg), and were either MF-exposed or sham-exposed for 14 weeks.