Search PubMed⌕ Search

Biomedical subjects

M Vergnes

Publications and source records attributed to M Vergnes.

At least 91 records · Page 5Linked to original sources
PubMed1990

Increased gamma-hydroxybutyric acid receptors in thalamus of a genetic animal model of petit mal epilepsy.

The distribution and kinetics of specific binding sites for gamma-hydroxybutyrate (GHB), a naturally occurring compound known to produce absence-like seizures, was studied in the brains of Wistar rats with spontaneous, bilaterally synchronous spike wave discharges (SWDs), a model of petit mal epilepsy, and non-epileptic controls using [3H]GHB autoradiography. [3H]GHB receptor binding was increased 40-60% in lateral thalamic nuclei of the epileptic animals. Kinetic analysis showed that the increase in the binding was due to an increase in density of low affinity GHB binding sites in the epileptic animals. Given the ability of GHB to produce petit mal-like seizures when administered to animals, and the fact that the SWDs in the Wistar rat model seem to emanate from lateral thalamus, these data raise the possibility that GHB-mediated mechanisms may play a role in the pathogenesis of petit mal seizures.

Animals↗
PubMed1989

Suppressive effects of intranigral injection of muscimol in three models of generalized non-convulsive epilepsy induced by chemical agents.

The involvement of intranigral gamma-aminobutyric acid (GABA) receptors in the control of generalized non-convulsive epilepsy was investigated in the rat in 3 models of petit mal epilepsy induced by systemic administration of gamma-butyrolactone, pentylenetetrazol and 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin 3-ol (THIP). Bilateral intranigral injection of muscimol (2 ng/0.2 microliters/side), a GABAA receptor agonist, significantly reduced the duration of EEG-recorded spike-and-wave discharges induced by gamma-butyrolactone (100 and 200 mg/kg i.p.), pentylenetetrazol (20 mg/kg i.p.) and THIP (7.5 mg/kg i.p.). This treatment had no effect on the electroencephalographic discharges observed after injection of THIP (10 mg/kg i.p.). Bilateral injection of muscimol (2 and 4 ng/side) into the substantia nigra did not modify the latency of onset nor the duration of clonic seizures induced by pentylenetetrazol at the dose of 40 mg/kg i.p. Bipolar depth electrode recording indicated that intranigral injection of muscimol did not alter nigral electroencephalographic activity. Autoradiography following intranigral injection of [3H]muscimol indicated a diffusion not exceeding 400 microns from the injection site. These results confirm that activation of GABA receptors in the substantia nigra suppresses the occurrence of spike-and-wave discharges in animal models of generalized non-convulsive epilepsy.

4-Butyrolactone↗
PubMed1989

Characterization of pretentorial periaqueductal gray matter neurons mediating intraspecific defensive behaviors in the rat by microinjections of kainic acid.

Unilateral microinjections of 40 pmol of kainic acid (KA; in 0.2 microliter) within the periaqueductal gray matter (PAG) evoked intraspecific defensive postures (defensive uprights, defensive alterting, defensive sideways, backing) in rats confronted with a conspecific. These reactions, which lasted for up to 30 min, were seemingly identical to the rat's natural defensive reaction to attacks by a conspecific although they were evoked by the investigatory approach, rather than the attack, of another rat. Histological analysis revealed that the strongest defensive reactions were evoked from sites within a restricted part of the pretentorial periaqueductal gray matter. Lower doses of KA induced fewer (20 pmol) or non-significant increases (4 pmol) in defensive reactions. Higher doses (100 and 200 pmol) increased the percentage of defensive behavior and also induced oriented jumps out of the test cage. In tests with a conspecific, defensive reactions were elicited most frequently when investigation by the partner was localized to the side of the body contralateral to the injection site. This was confirmed in a sensory reactivity test in which tactile stimulation by the experimenter elicited most defensive reactions when applied on the side of the body contralateral to the injection side. This test also revealed a somatotopic gradient in the animal's reaction: tactile stimulation of the contralateral head and the forelimb evoked the strongest reactions, whereas no responses were observed upon tactile stimulation of the contralateral flank or hindlimb. Measurement of electroencephalographic activity at the cortical, hippocampal, amygdala and PAG levels indicated that the evoked defensive reactions were not secondary to epileptogenic effects. Finally, quantitative analysis of an autoradiographic study found that [3H]KA diffused within a diameter of 1.0-1.2 mm around the cannula tip. Taken together, these results indicate the existence of a population of neurons within a restricted part of the pretentorial PAG of the rat, the excitation of which produces defensive responses and demonstrate that these defensive reactions have a socially adaptive value.

Animals↗
PubMed1988

Relationship between spike-wave discharges and vigilance levels in rats with spontaneous petit mal-like epilepsy.

The relationship between states of vigilance and spike and wave discharges (SWD) was examined during 12 hours in 4 Wistar rats from a strain bred for spontaneous generalized non-convulsant seizures. On the basis of cortical and hippocampal EEG and EMG activity, wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (REM) were distinguished. Of the SWD 86% occurred during quiet W, 14% during the first minutes of SWS. No SWD occurred during active wakefulness and they were exceptional during REM. These results show that the states of quiet W and transitional states favour the SWD in rats with petit mal-like epilepsy, as in human petit mal.

Animals↗
PubMed1988

Evidence that activation of GABA receptors in the substantia nigra suppresses spontaneous spike-and-wave discharges in the rat.

The involvement of intranigral gamma-aminobutyric acid (GABA) receptors in the control of generalized non-convulsive epilepsy was investigated in a genetically determined model of petit mal epilepsy in the rat. Bilateral intranigral injection of muscimol (2 ng/0.2 microliter/side), a GABA agonist, significantly suppressed EEG-recorded spike-and-wave discharges for about 80 min, both at the cortical and thalamic levels. This suppressive effect was shown to be dose-dependent, reproduced by bilateral intranigral injections of 4,5,6,7-tetrahydro-isoxazolo [5,4-c]pyridin 3-ol (THIP), another GABA agonist, and reversed by a subsequent intranigral injection of bicuculline methiodide, a GABA antagonist. In addition, the anti-absence effects of bilateral intranigral injections of muscimol were well localized to the substantia nigra. Bilateral intranigral injections of GABA antagonists per se had no effects on the discharges. These results demonstrate that activation of GABA receptors in the substantia nigra suppresses the occurrence of spike-and-wave discharges in an animal model of generalized non-convulsive epilepsy. The results are compared to data obtained in models of generalized convulsive epilepsy and the hypothesis of nigral GABAergic mechanisms as a control system for generalized epilepsies is discussed.

Animals↗
PubMed1988

Audiogenic seizures in Wistar rats before and after repeated auditory stimuli: clinical, pharmacological, and electroencephalographic studies.

A strain of Wistar rats was inbred for susceptibility to audiogenic seizures characterized by one or two wild running fits followed by tonic dorsiflexion with open mouth and then a catatonic state. During the tonic phase, the cortical EEG was flat for 1 to 2 sec, then changed to a slow, regular low-amplitude discharge, 9 to 12 c/s, for 25 to 60 sec. In these rats exposed to 40 daily 90-sec auditory stimuli, behavior and EEG changed. The wild running became disorganized by myoclonic jerks of the limbs and body. In some animals, the tonic extension disappeared and a myoclonic seizure developed progressively, with facial and forelimb clonus, and rearing and falling. In others, the tonic phase was followed by a generalized clonic phase. The EEG during the myoclonic and tonic-clonic seizures showed high-amplitude rhythmic spikes, polyspikes and spike-waves, 1 to 10 c/s, for 40 to 120 sec, often outlasting the sound stimulus. The effects of ethosuximide, carbamazepine and phenytoin were the same on primary and modified audiogenic seizures. The progressive behavioral and EEG modifications of audiogenic seizures following repeated auditory stimuli suggest that kindling had developed, the seizures being propagated from the brain stem to forebrain structures.

Acoustic Stimulation↗
PubMed1988

Evaluation of the anticonvulsant and biochemical activity of CGS 8216 and CGS 9896 in animal models.

CGS 8216, a benzodiazepine-receptor ligand with inverse agonistic properties, and CGS 9896, which possesses partial agonistic or mixed agonist-antagonist properties were compared in a number of epilepsy models. The effect of CGS 9896 on the decrease in GABA levels induced by isoniazid was also investigated. CGS 9896 inhibited the kindling process in rats in that it delayed the development of overt seizures and the increase in the duration of afterdischarges. In a genetic rat model characterized by absence-like EEG patterns, CGS 9896 dose-dependently suppressed these spontaneously occurring discharges, while CGS 8216 had no effect. However, CGS 8216 antagonized the anticonvulsant action of CGS 9896. CGS 9896 protected mice against seizures induced by beta-vinyllactic acid, whereas CGS 8216 shortened the latency period before convulsions occurred. CGS 9896 retarded the onset of convulsive fits caused by isoniazid without preventing the decrease in GABA levels produced by that drug. These results confirm the anticonvulsant activity of CGS 9896 and demonstrate the inverse agonistic activity of CGS 8216. The profile of CGS 9896 in the above tests suggests that it might be an effective anticonvulsant, primarily in absence-type seizures.

Animals↗
PubMed1988

Effects of drugs affecting dopaminergic neurotransmission in rats with spontaneous petit mal-like seizures.

Drugs interacting with dopaminergic neurotransmission were studied on a model of genetic petit mal-like seizures in a strain of Wistar rats. Dopamine participates in the control of seizures in this model, as in other models of petit mal or of genetic epilepsy. Mixed dopaminergic D1/D2 agonists: L-DOPA, apomorphine, amphetamine and nomifensine, gave dose-dependent reductions of the duration of spike and wave discharges. Mixed D1/D2 antagonists: haloperidol, flupentixol and pimozide, caused dose-dependent increases of duration of spike and wave discharges. The findings with specific agonists or antagonists of D1 or D2 receptors did not reveal clearly the respective roles of these receptors in controlling the spike and wave discharges. The D2 agonists, lisuride and pergolide, had no effect on spike and wave discharges, except at toxic doses; bromocriptine decreased the duration of the discharges, but without clear-cut dose-dependency. The D2 antagonists: sulpiride and tiapride, had no effect. The D1 agonist SKF 38393 decreased duration of the spike and wave discharges in a dose-dependent manner. The D1 antagonist SCH 23390 had a biphasic effect: increasing the duration of spike and wave discharges at small doses and decreasing it at large doses. These results suggest that the simultaneous stimulation or inhibition of both receptors, D1 and D2, is necessary for influencing spike and wave discharges in this model.

Animals↗
PubMed1988

Effects of gamma-hydroxybutyrate and gamma-butyrolactone derivates on spontaneous generalized non-convulsive seizures in the rat.

The effects of derivatives of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone were examined in Wistar rats from a strain in which spontaneous spike-and-wave discharges can be recorded electroencephalographically. For each compound, the effects were compared to those obtained in rats from a strain without spontaneous seizures. Administration of GHB (62.5-375 mg/kg, i.p.) increased, in a dose-dependent manner, the duration of spontaneous spike-and-wave discharges. In non-epileptic rats, this compound (250 and 375 mg/kg) induced bursts of spikes of a lower frequency and smaller amplitude than spontaneous spike-and-wave discharges. Similar results were obtained in both strains, respectively, after injection of gamma-butyrolactone (85-170 mg/kg, i.p.). This latter compound, however, showed greater potency in its epileptogenic effects than GHB. Administration of trans gamma-hydroxycrotonic acid (up to 1000 mg/kg, i.p.), a semi-rigid analogue of GHB was without any effect in both strains of rats. Injection of gamma-crotonolactone (42.5-170 mg/kg, i.p.), suppressed the spike-and-wave discharges in epileptic rats and had no effect in non-epileptic animals. These results confirm the similarities between seizures induced by GHB and spontaneous spike-and-wave discharges in the rat. The neural mechanism of the epileptogenic effect of GHB is discussed.

4-Butyrolactone↗
PubMed1988

Selective increase of offensive behavior in the rat following intrahypothalamic 5,7-DHT-induced serotonin depletion.

Cerebral serotonin (5-HT) depletions usually increase aggressive behaviors and more specifically facilitate elicitation of offensive behaviors. In order to localize the brain structures involved in this effect, 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin of 5-HT neurons, was injected into the ascending serotonergic pathway within the lateral hypothalamus, thus depleting 5-HT only in the forebrain structures. The effects of such treatment on offensive and defensive as well as social and non-social behaviors were studied in resident rats confronted with untreated intruders. Pretreatment with desipramine protected noradrenergic neurons. The content of 5-HT fell to 25% of controls, whereas noradrenaline was maintained at 90% in the forebrain anterior to the injection site. Ethological analysis of both resident's and intruder's behavior showed that offensive items were increased in 5,7-DHT-treated residents, whereas defensive items were increased in their non-treated partners; non-social activities were unchanged. Control of mouse-killing behavior during a 2-h test in the same animals showed a clear increase in elicitation of killing in 5,7-DHT-injected rats. These results confirm that the inhibitory control of serotonin is exerted specifically on offensive aggression. They suggest that forebrain structures are involved in this control.

5,7-Dihydroxytryptamine↗
PubMed1987

Effects of drugs affecting noradrenergic neurotransmission in rats with spontaneous petit mal-like seizures.

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.

Animals↗
PubMed1987

Spontaneous spike and wave discharges in thalamus and cortex in a rat model of genetic petit mal-like seizures.

In an inbred strain of Wistar rats, spontaneous spike and wave discharges (8 to 10 c/s) appeared regularly on the EEG during quiet wakefulness and were accompanied by an arrest of behavioral activity associated with vibrissal and facial myoclonia. These seizures were recorded over the entire neocortex, but predominantly in the frontoparietal cortex. Subcortical bipolar recordings in chronic preparations showed that the lateral thalamic nuclei were greatly involved in these discharges: high-voltage spike and waves always appeared either simultaneously with, or slightly before the cortical discharges. In some cases, thalamic discharges were not accompanied by cortical discharges. No discharges were recorded in medial thalamic nuclei, in the cingulate cortex, or in the hippocampus. These results confirm the thalamocortical prevalence in the development of these rats' petit mal-like seizures, with a possible driving from thalamic nuclei.

Animals↗
PubMed1987

Kindling of audiogenic seizures in Wistar rats: an EEG study.

The EEG of 20 Wistar rats inbred for audiogenic seizures was recorded during 40 daily auditory stimuli 90 s long. The first stimuli provoked wild running, with no cortical EEG abnormality, and then a tonic phase with a characteristic EEG of a brief flat trace 2 to 3 s long followed by low-amplitude regular activity, 10 to 12 c/s, lasting 40 to 60 s. The lack of paroxysmal EEG patterns suggests that the cortex plays only a minor role in audiogenic seizure development. After 5 to 15 daily stimuli, the EEG during the running period exhibited brief spike and spike-wave discharges preceding the EEG pattern of the tonic phase. After a few more daily stimuli these paroxysmal discharges progressively increased in amplitude and duration, overlapping with the regular activity of the tonic phase. After 20 to 30 stimuli, only high-amplitude spikes and spike-waves, 1 to 10 c/s, were seen for 40 to 120 s. The modified EEG persisted 2 to 4 months after daily stimulation was discontinued. Thus, with stimulus repetition, a paroxysmal discharge progressively involved cortical structures. These data suggest that repetition of audiogenic seizures induced a phenomenon related to kindling in Wistar rats susceptible to sound-induced epilepsy.

Acoustic Stimulation↗
PubMed1987

Bidirectional effects of beta-carbolines in rats with spontaneous petit mal-like seizures.

Seven benzodiazepine-receptor ligands of the beta-carbolines' group were administered IP in Wistar rats from (1) a strain displaying spontaneous petit mal-like seizures (PMLS) characterized by spike and wave discharges (SWD) and, (2) a strain where no seizure is ever observed (NS). Five different types of effects were observed. (1) Injection of a full agonist (ZK 93 423) suppressed SWD in PMLS rats, in a dose-dependent manner, and induced marked sedation with alteration of EEG background activity; (2) Injection of partial agonists (ZK 95 962, ZK 91 296) suppressed SWD in PMLS rats without sedation; (3) Injection of low doses of a full inverse agonist (DMCM) significantly increased the total duration of SWD in PMLS rats and induced SWD in NS rats. Higher doses of DMCM induced convulsions in both strains; (4) Injection of partial inverse agonists (FG 7142, ZK 90 886) aggravated SWD in PMLS and induced SWD in NS rats. FG 7142 induced convulsions only in PMLS animals, whereas no convulsions were ever observed with ZK 90 886; (5) Injection of an antagonist (ZK 93 426) did not significantly modify SWD in PMLS rats. However, this compound was able to reverse both antiepileptic effects of agonists and epileptogenic effects of inverse agonists. These results suggest the involvement of the benzodiazepine-GABA receptor complex in the control of petit mal-like seizures in rats.

Animals↗
PubMed1987

Kindling of audiogenic seizures in the rat.

A strain of Wistar rats was inbred in our laboratory for its susceptibility to sound. The seizures are characterized by one or two wild running fits which terminate in a tonic dorsiflexion with open mouth, followed by a catatonic state. During the tonic phase of the seizure, the cortical EEG is flattened for 2 to 3 s. Then, a slow and regular low-voltage (9-12 c/s) activity is observed during 40 to 60 s. When these animals are submitted to daily sound-stimulations, the behavioral as well as the EEG manifestations of the audiogenic seizures change progressively. After 5 to 30 exposures, the wild running becomes disorganized by occurrence of myoclonic jerks of the limbs and the body. In some animals, the tonic extension disappears and a myoclonic seizure develops progressively with facial and forelimb clonus, rearing and falling. In other animals, the tonic phase still occurs and is followed by a generalized clonic phase. During both the myoclonic and the tonicoclonic seizures, rhythmic spikes, polyspikes and spike and waves of high amplitude (1-10 c/s) during 40 to 120 s are observed on EEG recordings. These EEG modifications often outlast the sound stimulation. The pharmacological reactivity in rats exposed to single or repeated audiogenic seizures is similar: phenytoin and carbamazepine suppress both kinds of seizures at low doses whereas ethosuximide is efficacious only at high doses. In order to know whether the repeated exposure to sound or the repetition of seizures are responsible of the observed changes in audiogenic seizures, animals susceptible to sound were exposed daily to the seizure-inducing sound after previous injection of Diazepam, which prevented them from convulsing. On the other hand, sound susceptible animals were injected daily with a dose of PTZ inducing one or several convulsions without exposure to sound. None of these treatments ever facilitated the development of kindled audiogenic seizures. The progressive modification of behavioral and EEG modifications occurring when audiogenic seizures are repeated suggests that kindling has developed, the seizure extending from the brainstem to forebrain structures.

Acoustic Stimulation↗