Biomedical subjects

A Depaulis

Publications and source records attributed to A Depaulis.

At least 73 records · Page 4Linked to original sources

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↗

PubMed1990

The GABAergic nigro-collicular pathway is not involved in the inhibitory control of audiogenic seizures in the rat.

Involvement of the GABAergic nigro-collicular pathway in the control of audiogenic seizures was examined in genetically sensitive rats by studying the effects of bilateral injections into the substantia nigra of muscimol, a gamma-Aminobutyric acid (GABA) agonist, and those of bilateral injections into the superior colliculus of picrotoxin, a GABA antagonist, and of muscimol. Microinjections of muscimol (20-80 ng/side) into the substantia nigra and microinjections into the superior colliculus of picrotoxin (20 and 40 ng/side) both failed to suppress audiogenic seizures. Following injections into the superior colliculus, audiogenic seizures were in fact facilitated by picrotoxin and suppressed by muscimol. These results suggest that the nigro-collicular GABAergic pathway is not involved in the inhibitory control over audiogenic seizures. Conversely, a different GABAergic mechanisms may be involved in the superior colliculus in the control of this form of epilepsy.

Acoustic Stimulation↗

PubMed1990

Immediate effects of 14 non MAOI antidepressants in rats with spontaneous petit mal-like seizures.

1. Wistar rats of a strain presenting spontaneous petit mal-like seizures were injected intraperitoneally with graded doses of 14 non-monoamine oxidase inhibitor antidepressants and the immediate effects on behavior and the EEG were recorded. 2. Amineptine and nomifensine, the two drugs interacting with dopaminergic neurotransmission, reduced the duration of spontaneous spike-wave discharges (SWD) and were thus potentially antiepileptic. 3. Trazodone increased SWD duration. 4. The antidepressants, imipramine-like (imipramine, chlorimipramine, desipramine, metapramine and amitriptyline) and non-imipraminic (minaprine, maprotiline, viloxazine, mianserin, fluvoxamine and indalpine), and the 3 noted above, had potentially convulsive effects.

Animals↗

PubMed1990

Involvement of the nigral output pathways in the inhibitory control of the substantia nigra over generalized non-convulsive seizures in the rat.

Activation of GABAergic transmission within the substantia nigra has been shown to suppress several forms of generalized seizures in experimental models of epilepsy. More especially, such pharmacological manipulations suppress spontaneous and chemically-induced generalized non-convulsive seizures in the rat. The aim of the present study was to examine the role of the dopaminergic and GABAergic thalamic and collicular nigral outputs in this antiepileptic effect. For this purpose, we examined the effects of output destruction on the antiepileptic effect of intranigral injections of a GABA agonist or pharmacological blockade of the neurotransmission at the nerve terminal level in rats with spontaneous absence seizures. After selective destruction of dopaminergic neurons within the substantia nigra with 6-hydroxydopamine (5 micrograms/side) or hemisection of the ascending nigral output, bilateral intranigral injection of muscimol (2 ng/side) still significantly suppressed generalized non-convulsive seizures. Bilateral lesioning of the ventromedial nucleus of the thalamus did not abolish the antiepileptic effects of intranigral muscimol (2 ng/side) and the GABA antagonist, picrotoxin, when given into this thalamic nucleus (10 ng/side) also failed to induce suppression of spike and wave discharges. The antiepileptic effects of intranigral injection of muscimol (2 ng/side) was reversed by bilateral electrolytic lesions of the superior colliculus. Blockade of the GABAergic transmission at this level with picrotoxin (40 ng/side) significantly suppressed generalized non-convulsive seizures. Finally, excitation of collicular cell bodies with low doses of kainic acid (4 and 8 ng/side) also resulted in a suppression of spike and wave discharges. These results demonstrate that the GABAergic nigrocollicular pathway is critical for the inhibitory control of the substantia nigra over generalized non-convulsive seizures. The data further suggest that antiepileptic effects observed following potentiation of GABAergic transmission in the substantia nigra result from a disinhibition of collicular cell bodies.

Animals↗

PubMed1990

Suppression of spontaneous generalized non-convulsive seizures in the rat by microinjection of GABA antagonists into the superior colliculus.

Intranigral injections of GABA agonists suppress spontaneous and chemically induced generalized non-convulsive seizures in the rat. In order to examine whether the GABAergic nigrotectal pathway could be involved in this suppression, bilateral injections of GABA antagonists were performed in the superior colliculus of rats with spontaneous generalized non-convulsive seizures. Bilateral microinjections into this structure of the GABA antagonists picrotoxin (20 and 40 ng/side) and bicuculline methiodide (5 ng/side) suppressed spike-and-wave discharges for 40 min and 20 min post injection, respectively. Unilateral injections of picrotoxin (40 ng) into the superior colliculus as well as bilateral injections of a GABA agonist (muscimol; 80 ng) did not induce significant modifications. These results show that blockade of the GABAergic transmission at the level of the superior colliculus results in a suppression of generalized non-convulsive seizures. These data support the hypothesis that the suppressive effect of intranigral injections of GABA agonists over generalized non-convulsive seizures involves, at least in part, the nigrotectal GABAergic pathway.

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

Anticonvulsant effect of muscimol injected into the thalamus of spontaneously epileptic Mongolian gerbils.

Injections of muscimol (12.5 or 25 ng bilaterally), a GABAA agonist, into the posterior nuclei of the thalamus suppressed generalized convulsive seizures in the spontaneously epileptic Mongolian gerbil. This anticonvulsant effect was dose-dependent and was reversed by picrotoxin (10 ng bilaterally), a GABAA antagonist. Bilateral intrathalamic injections of 1-baclofen (50 ng), an agonist of the GABAB receptor, were ineffective in suppressing seizures in this model. These results suggest that GABAergic transmission within the thalamus is involved in the control or the genesis of some generalized convulsive seizures.

Animals↗

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

Relationship between analgesia and cardiovascular changes induced by electrical stimulation of the mesencephalic periaqueductal gray matter in the rat.

Analgesia and cardiovascular changes produced by electrical stimulation of the midbrain periaqueductal gray matter were examined in the lightly pentobarbital-anesthetized rat. The current intensity required to elicit analgesia was first determined, using the tail-flick test, after which the effects on arterial pressure and heart rate were recorded from stimulating at the same intensity. Intensity thresholds for decreases and/or increases in arterial pressure were also ascertained at the same sites. Although stimulation at the analgesia threshold produced increases in arterial pressure at more than 60% of the sites within the periaqueductal gray, decreases, no change, and mixed responses were also observed. Below the periaqueductal gray, increases in arterial pressure occurred at analgesia threshold for more than 70% of the sites studied, and no cardiovascular changes were found for 20% of the sites. Above the periaqueductal gray, no change and mixed responses were the predominant effects at analgesia threshold. A correlation across sites within the periaqueductal gray was found between the threshold for stimulation-produced analgesia and the threshold for a change in arterial pressure. No reliable alterations in heart rate were observed at any stimulation site. These results are in agreement with the existence of a common midbrain substrate for both the regulation of pain inhibition and cardiovascular function. However, they indicate that analgesia resulting from stimulation of the periaqueductal gray matter does not necessarily occur concurrently with an increase in arterial pressure.

Analgesia↗

PubMed1988

Elicitation of intraspecific defence reactions in the rat from midbrain periaqueductal grey by microinjection of kainic acid, without neurotoxic effects.

Microinjection of 40 pmol of the neuroexcitotoxin, kainic acid (KA) in the midbrain periaqueductal grey region (PAG) evoked a significant increase in both defensive and immobile behaviours in rats tested in a social situation. The evoked reactions appeared identical to the rat's natural defensive reaction to attack by a conspecific, although they were evoked by the presence, rather than the attack, of another rat. The long duration and natural appearance of the KA-evoked reactions stand in contrast to the short, 'explosive' reactions evoked by injection in the PAG of other excitant amino acids. There was no behavioural evidence of a diminution in the effect of repeated injections of KA in the PAG, nor was there any histological evidence of neurotoxicity.

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

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

GABAergic modulation of the analgesic effects of morphine microinjected in the ventral periaqueductal gray matter of the rat.

The possibility that GABAergic neurons in the ventral periaqueductal gray matter modulate the analgesic effects of morphine microinjected into this brain area was investigated in the rat. Microinjection of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin 3-ol (THIP) (0.4 microgram in 0.2 microliter), a GABA agonist, in the ventral periaqueductal gray matter significantly reversed the increase of tail-flick latency induced by a prior injection of morphine sulfate (4 micrograms in 0.2 microliter) at the same site. Conversely, microinjection in the same region of picrotoxin (10 ng in 0.2 microliter), a GABA antagonist, significantly potentiated the analgesic effect of the same dose of morphine. These results suggest the existence of GABAergic neurons that tonically inhibit periaqueductal gray output neurons involved in centrifugal pain inhibition. The analgesic effects of opiates may, at least in part, result from disinhibition of these GABAergic neurons.

Animals↗

PubMed1987

Diazepam dissociates the analgesic and aversive effects of periaqueductal gray stimulation in the rat.

Electrical stimulation of the periaqueductal gray matter (PAG) of the rat can produce both analgesia and aversive reactions. To determine if these two effects can be dissociated, diazepam, a benzodiazepine, was administered to rats chronically implanted with electrodes in the PAG. The threshold for stimulation-produced analgesia or aversion, whichever was lowest, was determined before and after drug administration. Diazepam (1 mg/kg) attenuated stimulation-produced aversive reactions at 12 of 20 stimulation sites, allowing analgesia to be measured at the same threshold. Diazepam did not alter baseline pain sensitivity or thresholds for stimulation-produced analgesia. These results indicate that aversive reactions and analgesia from PAG stimulation can be pharmacologically dissociated.

Analgesia↗