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Biomedical subjects

A Depaulis

Publications and source records attributed to A Depaulis.

At least 19 recordsLinked to original sources
PubMed1992

The GABAA receptor complex in experimental absence seizures in rat: an autoradiographic study.

The regional distribution of radioactive ligand binding for different receptors of the gamma-aminobutyric acid A (GABAA)-benzodiazepine-picrotoxin chloride channel complex was measured on tissue section by autoradiography in brains taken from a genetic strain of Wistar rats with spontaneous absence-like seizures, the genetic absence epilepsy rats from Strasbourg (GAERS), and a control colony. The ligands employed included [3H]muscimol for high affinity GABA agonists sites; [3H]SR 95531 for the low-affinity GABA sites; [3H]flunitrazepam for the benzodiazepine sites; and [35S]t-butyl bicyclophosphorothionate (TBPS) for the picrotoxin site. There was no significant change between GAERS and control animals in [3H]flunitrazepam and [35S]TBPS binding. However, there was significantly decreased [3H]muscimol and [3H]SR 95531 binding in the CA2 region of the hippocampus of the GAERS. This was due to a decrease in Bmax of both [3H]muscimol and [3H]SR 95531 binding in the epileptic strain.

Animals↗
PubMed1992

Dorsal tegmentum kindling in rats.

Electrical stimulations were applied daily for 40 days to the dorsal tegmentum in 9 rats through chronically implanted bipolar electrodes. The intensity of current (2 s trains of 50 Hz, 1 ms monophasic square waves) necessary to trigger a full tonic seizure was determined and applied for all further stimulations. Initial stimulations induced a tonic seizure with a low voltage fast electrocorticographic activity. After repeated stimulations, high amplitude spike and wave discharges developed over the cortex, their duration exceeding 50 s at the 40th stimulation. Simultaneously, the tonic seizures evolved into tonic-clonic fits with bilateral myoclonias following the tonic phase. These EEG and behavioral modifications persisted for 30 days after the last stimulus. These results demonstrate that kindling may be obtained from brainstem structures.

Animals↗
PubMed1992

Genetic absence epilepsy in rats from Strasbourg--a review.

We have selected a strain of rats and designated it the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). In this strain, 100% of the animals present recurrent generalized non-convulsive seizures characterized by bilateral and synchronous spike-and-wave discharges accompanied with behavioural arrest, staring and sometimes twitching of the vibrissae. Spontaneous SWD (7-11 cps, 300-1,000 microV, 0.5-75 sec) start and end abruptly on a normal background EEG. They usually occur at a mean frequency of 1.5 per min when the animals are in a state of quiet wakefulness. Drugs effective against absence seizures in humans (ethosuccimide, trimethadione, valproate, benzodiazepines) suppress the SWD dose-dependently, whereas drugs specific for convulsive or focal seizures (carbamazepine, phenytoin) are ineffective. SWD are increased by epileptogenic drugs inducing petit mal-like seizures, such as pentylenetetrazol, gamma-hydroxybutyrate, THIP and penicillin. Depth EEG recordings and lesion experiments show that SWD in GAERs depend on cortical and thalamic structures with a possible rhythmic triggering by the lateral thalamus. Most neurotransmitters are involved in the control of SWD (dopamine, noradrenaline, NMDA, acetylcholine), but GABA and gamma-hydroxybutyrate (GHB) seem to play a critical role. SWD are genetically determined with an autosomal dominant inheritance. The variable expression of SWD in offsprings from GAERS x control reciprocal crosses may be due to the existence of multiple genes. Neurophysiological, behavioural, pharmacological and genetic studies demonstrate that spontaneous SWD in GAERS fulfill all the requirements for an experimental model of absence epilepsy. As the mechanisms underlying absence epilepsy in humans are still unknown, the analysis of the genetic thalamocortical dysfunction in GAERS may be fruitful in investigations of the pathogenesis of generalized non-convulsive seizures.

Action Potentials↗
PubMed1992

The inhibitory control of the substantia nigra over generalized non-convulsive seizures in the rat.

A system exerting inhibitory control over generalized epilepsies and involving neurons from the substantia nigra has been described by several authors in experimental models of convulsive seizures. In the present study, the existence of such a control system governing absence epilepsy was investigated using models of non-convulsive seizures in the rat. Activation of the GABAergic neurotransmission within the substantia nigra by local injection of GABA agonists (muscimol, THIP) or an inhibitor of GABA degradation (gamma-vinyl GABA) suppresses generalized non convulsive seizures, whether they are genetically determined or induced by systemic injections of gamma-butyrolactone (100 and 200 mg/kg), pentylenetetrazole (20 mg/kg) or THIP (7.5 mg/kg). The ascending dopaminergic nigral output or the GABAergic fibres to the ventromedial thalamus are not critically involved in this control system. By contrast, the GABAergic nigro-collicular pathway appears crucial: bilateral lesion of the superior colliculus abolishes the anti-epileptic effects of intranigral injection of muscimol and blockade of the GABAergic transmission within the superior colliculus results in a suppression of generalized non-convulsive seizures. Finally, activation of collicular cell bodies by low doses of kainic acid significantly suppresses absence seizures. These results suggest the existence of a control system inhibiting generalized non-convulsive seizures which is activated by the release of the tonic inhibition exerted by the nigral GABAergic fibres on collicular neurons. The similarities between this system and the control system described for convulsive seizures are discussed.

Animals↗
PubMed1992

Longitudinal neuronal organization of defensive reactions in the midbrain periaqueductal gray region of the rat.

In a previous study we investigated the intraspecific defensive reactions evoked by excitation of neurons in the intermediate third of the midbrain periaqueductal gray matter (PAG) of the rat. Experiments revealed that activation of neurons in this region of the PAG mediated: (i) backward defensive behavior, characterized by upright postures and backward movements, and (ii) reactive immobility ("freezing"), in which the rat remained immobile, but reacted with backward defensive behavior to investigative, non-aggressive contact initiated by the partner. In the present study, we aimed to extend our understanding of PAG mediation of defensive behavior by observing: (i) in a non-aggressive social interaction test, the behavioral effects of microinjections of low doses of kainic acid (40 pmol in 200 nl) made in the caudal third of the PAG; and (ii) the behavioral and cardiovascular effects of microinjections of D,L-homocysteic acid (5-10 nmol in 50-100 nl) made in the PAG of the unanesthetized decerebrate rat. Kainic acid injections into the area lateral to the midbrain aqueduct in the caudal third of the PAG evoked: (i) forward avoidance behavior, characterized by forward locomotion and occasional hop/jumps; (ii) reactive immobility ("freezing"), in which the rat remained immobile, but reacted with forward avoidance behavior to investigative, non-aggressive contact initiated by the partner; and (iii) 22-28 kHz ultrasonic vocalizations. These injections also evoked a dramatic increase in defensive responsiveness to tactile stimuli on the half of the body contralateral, but not ipsilateral, to the site of injection. Electroencephalographic measurements indicated that none of these effects were secondary to seizure activity. In the decerebrate rat, D,L-homocysteic acid injections in the caudal third of the PAG evoked forward running movements along with increased blood pressure and heart rate, the strongest effects being evoked from the region lateral to the midbrain aqueduct. More rostrally, sites in the intermediate PAG evoked backward "defensive" movements, which were also associated with increased blood pressure and heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Aggression↗
PubMed1992

Opposite effects of pentylenetetrazol on self-defensive and submissive postures in the rat.

In a previous work, using the resident-intruder situation, we have shown that a benzodiazepine inverse agonist could exert a "fear-promoting" effect, in decreasing self-defensive behaviours while increasing submissive postures. To further test this hypothesis, the effects of pentylenetetrazol on different forms of defensive behaviour were examined in male intruder rats confronted with offensive residents. Administration of pentylenetetrazol (10 and 20 mg/kg, IP) increased submissive postures such as immobility and on-the-back, but reduced self-defensive postures. Other active behaviours were not reduced, thus excluding a non-specific behavioural suppression. These results suggest that self-defensive and submissive behaviours can be dissociated and that anxiogenic compounds are more likely to increase submissive behaviours than self-defensive ones.

Aggression↗
PubMed1992

Involvement of intrathalamic GABAB neurotransmission in the control of absence seizures in the rat.

The role of intrathalamic GABAB neurotransmission in the control of absence seizures was investigated. In rats with genetic absence epilepsy, bilateral injections of R-baclofen (50, 100 and 200 ng/side), a selective GABAB receptor agonist, into the specific relay nuclei and the reticular nuclei of the thalamus increased spontaneous spike and wave discharges in a dose-dependent fashion, whereas injections of a GABAB antagonist CGP 35,348 (1, 2.5 and 5 micrograms/side) into the same sites decreased these seizures dose-dependently. The effect of R-baclofen (200 ng/side) on spike and wave discharges could be blocked by a subsequent injection of CGP 35,348 (1 microgram/side) at the same site. Injections of R-baclofen (200 ng) or CGP 35,348 (5 micrograms) into the midline thalamus had no effect on these seizures. In non-epileptic rats, bilateral injections of R-baclofen (1 microgram/side) into the specific relay nuclei induced synchronized rhythmic oscillations on the cortical electroencephalogram. The results suggest that GABAB receptors in the ventrolateral thalamus and in the reticular nuclei are involved in an oscillatory activity which underlies the rhythmic spike and wave discharges recorded during spontaneous generalized non-convulsive seizures.

Animals↗
PubMed1992

Positive transfer of audiogenic kindling to electrical hippocampal kindling in rats.

Audiogenic seizures in genetically susceptible rodents are provoked by intense acoustic stimulations which result in a tonic seizure associated with a short flattening of the EEG. These seizures have been shown to involve primarily brainstem structures. Daily exposure to sound for 30-40 days produced a permanent change in the evoked seizure with development of facial myoclonias, rearing and falling, or of tonic-clonic seizures accompanied by high amplitude cortical spike-and-wave discharges. Kindled audiogenic seizures appear similar to seizures kindled from amygdala or hippocampus, suggesting that repeated auditory stimulations cause a progressive propagation of the epileptic discharge toward limbic structures. To verify this hypothesis, the behavioral and EEG development of electrical hippocampal kindling has been studied in 7 non epileptic controls (NE), 8 acoustic susceptible (AS), and 8 audiogenic kindled rats (KAS). The behavioral and EEG development of the electrical hippocampal kindling was similar in the AS and the NE rats. However, 2 animals in the AS group but no controls exhibited behavioral running and bouncing during the course of hippocampal kindling. In the KAS group, the hippocampal kindling was clearly facilitated as compared to NE and AS: behavioral stage greater than or equal to 5 was reached in a mean of 4 stimulations in KAS versus 30 and 22 stimulations respectively in NE and AS groups. This positive transfer phenomenon suggests that during kindling of audiogenic seizures, epileptic discharge spreads from the brainstem to the forebrain and progressively involves the hippocampus.

Acoustic Stimulation↗
PubMed1991

Intrathalamic injections of gamma-hydroxybutyric acid increase genetic absence seizures in rats.

The effects of intrathalamic injections of gamma-hydroxybutyric acid (GHB) and of NCS 382 85, a specific antagonist of GHB receptors, were evaluated in rats with spontaneous generalized absence epilepsy. Bilateral injections of GHB (25 and 50 micrograms/side) into the mediolateral thalamus increased spontaneous spike and wave discharges (SWD) in a dose-dependent fashion. This effect was suppressed by administration of NCS 382 85 (50 micrograms/side). Bilateral injection of NCS 382 85 alone (50 and 100 micrograms/side) into the same sites had no effect on SWD duration. Injection of GHB or NCS 382 85 into the midline thalamus and the area of reticular nuclei did not modify the SWD. These data suggest that GHB receptors in the mediolateral thalamus may be involved in the control of spontaneous SWD in this rat model of petit mal epilepsy.

Animals↗
PubMed1991

Evidence for a critical role of GABAergic transmission within the thalamus in the genesis and control of absence seizures in the rat.

The involvement of GABAergic transmission within the thalamus in the generation and control of spike and wave discharges (SWD) in generalized non-convulsive or absence epilepsy was studied in rats with spontaneous SWD and in non-epileptic rats. In epileptic rats, bilateral injections of gamma-vinyl GABA (GVG, 10 micrograms/side) or muscimol (10 ng/side) into the medial part of the ventral lateral thalamus, i.e. the specific relay nuclei, significantly increased spontaneous cortical SWD whereas similar injections into the most lateral part of the thalamus, i.e. the area of the reticular nuclei, significantly suppressed these seizures. Injections of GVG (20 micrograms) or muscimol (20 ng) into the midline thalamus had no direct effect on the spontaneous SWD. In non-epileptic rats, injections of GVG (25 micrograms/side) or muscimol (100 ng/side) into the thalamic relay nuclei produced short SWD on the cortical EEG. These results suggest that GABAergic neurons in the reticular nuclei and their projections to the specific relay nuclei of the thalamus are involved in the elicitation and control of generalized non-convulsive seizures.

Aminocaproates↗
PubMed1991

Opposite effects of agonist and inverse agonist ligands of benzodiazepine receptor on self-defensive and submissive postures in the rat.

The effects of benzodiazepine receptor ligands on different types of defensive behaviours were examined in intruder male rats confronted with offensive residents. Chronic administration, via a subcutaneous silastic pellet, of a full agonist (diazepam) for 15 days increased self-defensive postures as well as social and non-social behaviour whereas submissive postures and flight were reduced. Acute administration of a partial agonist (ZK 91296) resulted in a similar increase in self-defensive postures and a decrease of submission and non-social elements. Acute administration of a partial inverse agonist (FG 7142) reduced defensive postures and social behaviour whereas submissive postures were increased. These results show that activation of benzodiazepine receptors by full or partial agonists increased self-defensive responses to attacks by a conspecific, while decreasing submissive postures. On the contrary, "inverse activation" of these receptors by an inverse agonist increased submissive postures while decreasing self-defensive responses. These data suggest that benzodiazepine receptors are involved in the control of the animal's strategy to respond to an attack of another rat.

Aggression↗
PubMed1991

Lesions of noradrenergic neurons in rats with spontaneous generalized non-convulsive epilepsy.

The role of noradrenergic neurons in the control of a spontaneous generalized non-convulsive epilepsy (GNCE) was investigated. In rats with genetic spontaneous absence seizures, we produced lesions using 2 neurotoxins: 6-hydroxydopamine (6-OHDA) and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). Lesions of noradrenergic neurons were made either in pups by neonatal 6-OHDA intraperitoneal (i.p.) injection (2 x 100 mg/kg) or in adult rats by i.p. administration of DSP4 (60 mg/kg) or bilateral microinjection of 6-OHDA in the locus coeruleus (LC) (4 micrograms/microliters, 2 microliters/side). Effectiveness of the lesions was controlled by measuring dopamine (DA) and noradrenaline (NA) contents in the brains. Neonatal 6-OHDA administration did not lead to any difference in seizures in adult animals, compared with control rats. DSP4 injections and LC lesions with local injections of 6-OHDA produced a transient increase of the seizures. Within one to two weeks, the seizure duration went back to prelesion levels. No seizure occurred when the same lesions were performed in non epileptic rats. These results suggest that NA is not involved in the genesis of this generalized non-convulsive epilepsy; they confirm that NA participates in the control of seizures in this model, but the rapid development of compensatory mechanisms shows that this control is not critical.

Animals↗
PubMed1991

Are rats with genetic absence epilepsy behaviorally impaired?

Absence seizures in humans are characterized by unresponsiveness to external stimuli and inactivity. However, in typical generalized non-convulsive epilepsy in children, intellectual capacities are considered to be normal. Wistar rats from an inbred strain with spontaneous absence-like seizures were compared with rats from the outbred control strain in various behavioral tasks in order to detect possible impairments related either to the absence epilepsy or to occurrence of spike and wave discharges (SWD). Spontaneous circadian locomotion, exploratory activity in an open field, social interactions with an unfamiliar conspecific and mouse killing behavior were similar in both strains. Avoidance learning in a shuttle box or food reinforced learning in a Skinner test were unimpaired or even improved in epileptic rats. During performance of a learned task either in the Skinner box or in a conditioned sound-bar pressing task, SWD were suppressed in epileptic rats as long as they were working for reinforcement. SWD reappeared when the motivation to perform the task had declined: unresponsiveness to a conditioned stimulus was then observed during SWD. These data are in agreement with observations commonly described in children with typical genetic absence epilepsy.

Aggression↗
PubMed1990

Mapping of spontaneous spike and wave discharges in Wistar rats with genetic generalized non-convulsive epilepsy.

Electrical activity was recorded in different parts of the brain in Wistar rats from a strain with genetic generalized non-convulsive epilepsy (GNCE or absence epilepsy). Movable bipolar electrodes were lowered stereotaxically by 1 mm steps into the brain in immobilized animals. Spontaneous spike and wave discharges (SWD) of the largest amplitude were recorded in the cortex and in lateral nuclei of the thalamus where they appeared occasionally to precede. Smaller amplitude SWD were recorded in the striatum, hypothalamus, tegmentum and substantia nigra. No SWD were recorded in limbic structures. Partial limbic seizures induced by the introduction of the electrode did not interfere with occurrence of cortical SWD. These results confirm the primacy of thalamocortical involvement in SWD of GNCE. The absence of spread to limbic structures and the implication of a precisely limited substrate in GNCE accounts for the clinical and pharmacological specificity of this particular kind of epilepsy.

Animals↗
PubMed1990

Potentiation of gamma-vinyl GABA (vigabatrin) effects by glycine.

Vigabatrin, because of its ability to increase brain GABA concentration, acts as an anticonvulsant on convulsive epileptic seizures and increases seizures in generalized non-convulsive epilepsy. Next to GABA, glycine is one of the most important inhibitory neurotransmitter amino acids. We studied the influence of glycine on the effects of treatment with vigabatrin in two rat models of generalized convulsive seizures and a rat model of spontaneous generalized non-convulsive seizures. Glycine (750 mg/kg i.p.) or vigabatrin (200 mg/kg i.p.), when given alone, provided partial protection against convulsive seizures, while combined treatment with the two drugs significantly suppressed the convulsive seizures in both the mercaptopropionic acid (MPA)-induced seizures and audiogenic seizures. In contrast to the response to treatment with each individual drug, the drug combination nearly abolished the appearance of isolated spikes on the EEG in MPA seizures. On the other hand, glycine also enhanced the aggravating effect of vigabatrin on spontaneous spike and wave discharges in a rat model of genetic absence epilepsy, whereas glycine or vigabatrin alone, at the above doses, produced only a slight, non-significant increase in spontaneous spike and wave discharges. The GABA-glycine interaction is the first example of a synergistic action of two inhibitory neurotransmitters on seizure-related pathological discharges.

3-Mercaptopropionic Acid↗