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Biomedical subjects

A Depaulis

Publications and source records attributed to A Depaulis.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1986

Elicitation of intraspecific defensive behaviors in the rat by microinjection of picrotoxin, a gamma-aminobutyric acid antagonist, into the midbrain periaqueductal gray matter.

Behavioral reactions induced in the rat by microinjections of a gamma-aminobutyric acid (GABA) antagonist (picrotoxin; 25 and 50 ng in 0.25 microliter) into the midbrain periaqueductal gray matter were measured in an open-field test and when the animal was confronted by a conspecific introduced into its cage (i.e. resident-intruder paradigm). In the open-field, microinjections of picrotoxin significantly increased backward locomotion while decreasing self-grooming. In the resident-intruder paradigm, microinjections of picrotoxin selectively increased defensive reactions (defensive uprights, defensive sideways, retreat) while offensive behaviors were rather reduced. In addition, the actual nature of the effects was found to depend upon the intruder's relative position. Defensive reactions were significantly increased when the partner was on the side contralateral to the injection site, whereas social approach behaviors (fur investigation, anogenital investigation) were decreased when the partner was located on the ipsilateral side. These data suggest the involvement of GABAergic synapses within the midbrain periaqueductal gray matter in the control of intraspecific defensive behaviors in the rat.

Aggression↗
PubMed1986

Parachlorophenylalanine-induced serotonin depletion increases offensive but not defensive aggression in male rats.

Cerebral 5-HT depletion has been shown to facilitate elicitation of various kinds of aggressive behavior in rats. The question as to whether both offensive and defensive aggressive reactions are affected to the same extent was examined in a resident-intruder paradigm where an ethological analysis of the two animals allows an evaluation of non-social activities as well as agonistic interactions, including both offense and defense. PCPA (375 mg/kg IP) was administered either to the resident or the intruder and the interactions with an untreated conspecific were recorded in the resident's home cage for an 8 min period three days after injection when 5-HT was maximally reduced. PCPA treatment increased the occurrence of social approach and offensive postures in resident rats, whereas their untreated partners displayed more defensive reactions. When intruders were injected, only non-significant increases in approach and offense were observed. In no case did PCPA affect occurrence of defensive postures in the injected animals. These results confirm that serotonin plays a role in controlling offensive aggression but not defensive behavior.

Aggression↗
PubMed1986

Ontogeny of spontaneous petit mal-like seizures in Wistar rats.

Wistar rats spontaneously presenting electroclinical signs of petit mal-like epileptic seizures were inbred until all offspring were affected, and the ontogeny of this inherited phenotype was studied in the offspring from 30-60 days of age to 18 months. The first EEG spike and wave discharges appeared at 40-120 days. Their number and duration increased progressively with age.

Aging↗
PubMed1986

Involvement of brain opiate receptors in the immune-suppressive effect of morphine.

We previously reported that a single systemic injection of a high dose of morphine (greater than or equal to 20 mg/kg) transiently suppresses splenic natural killer cell cytotoxicity in rats. The present study examined the possibility that the immune-suppressive effect of morphine is mediated by opiate receptors in the brain. Supporting this hypothesis, we found that morphine (20 or 40 micrograms) injected into the lateral ventricle suppressed natural killer cell activity to the same degree as a systemic dose higher by three orders of magnitude. This effect was blocked by an opiate antagonist, naltrexone. Natural killer cell activity was unaffected by systemic administration of N-methyl morphine, a morphine analogue that does not cross the blood-brain barrier. These data implicate opiate receptors in the brain in morphine-induced suppression of natural killer cell cytotoxicity.

Animals↗
PubMed1985

Elicitation of conspecific attack or defense in the male rat by intraventricular injection of a GABA agonist or antagonist.

The involvement of central GABAergic mechanisms in the control over offensive and defensive behaviours in the rat was studied using intracerebroventricular injections (5 microliter) of a GABA agonist (THIP) or a GABA antagonist (bicuculline methiodide). Intracerebroventricular injections of THIP (1.25 and 2.5 micrograms) induced attacks and offensive sideways towards an untreated partner, in animals placed in a neutral area where no aggressive reactions occur in controls. Social approach behaviours (partner investigation, allogrooming) were also increased in both attacking and non-attacking animals, whereas individual behaviours (cage exploration, autogrooming, immobile posture) were decreased. Inversely, intracerebroventricular injections of bicuculline methiodide (62.5 and 125 ng) suppressed offensive items (attacks, offensive sideways, upright postures) in resident animals confronted with untreated intruders and increased occurrence of defensive sideways. This treatment also decreased reactions oriented towards the partner (investigation, allogrooming and crawl under/over), while increasing individual behaviours (cage exploration, immobile posture). These data demonstrate that activation of central GABA receptors elicits intraspecific offensive behaviours in the rat. On the contrary, blockage of these receptors induces defensive reactions and suppresses offensive behaviours. The involvement of these receptors in the neural control over aggressive behaviour in the rat is discussed.

Aggression↗
PubMed1985

Identification of midbrain neurones mediating defensive behaviour in the rat by microinjections of excitatory amino acids.

Unilateral microinjections (0.20 microliter) of excitatory amino acids were made into the midbrain of freely moving rats. Injections made within the midbrain periaqueductal grey matter (PAG) consistently elicited reactions characteristic of defensive behaviour (i.e. explosive jumps, freezing, upright postures), whereas injections made in the tegmentum bordering the PAG did not as reliably elicit such behaviour. As injections of excitatory amino acids depolarize cell bodies but not axons, the results suggest that a population of neurones whose excitation elicits these reactions is found primarily within the midbrain PAG of the rat. Furthermore, the data suggested that such neurones may be localized preferentially within the caudal half of the midbrain PAG. Injections of the GABA antagonist, bicuculline methiodide, at many of the same midbrain sites produced behaviour similar to that elicited by excitatory amino acids indicating a possible GABAergic modulation of these same PAG-mediated reactions. It also was observed following unilateral injection into the PAG, of either the excitatory amino acid, L-aspartic acid or bicuculline, that defensive behaviour was elicited by touching the rat on the body or snout contralateral but not ipsilateral to the injection site. This suggests that the induction of defensive behaviour by unilateral PAG stimulation is due, at least in part, to lateralized alterations in sensorimotor responsiveness.

Amino Acids↗
PubMed1985

Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat.

One-third of Wistar rats bred in our laboratory present recurrent seizures whose EEG and clinical symptomatology resemble those of human petit mal. Bilateral cortical synchronous spike- and wave discharges (7-11 c/s; 200-600 microV, lasting 0.5 to 40 s) accompany behavioral arrest and are associated frequently with facial myoclonia. These seizures, observed as long as the animals survive, appear spontaneously and seem to be unrelated to surgical procedures. Antiepileptics in common clinical use were tested. Ethosuximide (greater than 12.5 mg/kg), diazepam (greater than 0.5 mg/kg), trimethadione and sodium valproate (greater than 50 mg/kg) suppressed these discharges in a dose related manner. Carbamazepine and phenytoin were ineffective or aggravated the seizures. Phenobarbital, effective at 2.5 to 10 mg/kg, was ineffective at 20 mg/kg. The similar effects of these antiepileptics on both the rats' seizures and human petit mal confirm the hypothesis that this phenomenon constitutes a valid pharmacological model of petit mal epilepsy. Its predictive value appears to be superior to that of other currently used models.

Animals↗
PubMed1984

Biphasic effects of Ro 15-1788 on spontaneous petit mal-like seizures in rats.

The effects of various doses of the potent and specific benzodiazepine antagonist Ro 15-1788 were investigated in rats with spontaneous non convulsive, petit mal-like seizures. In preliminary experiments, Ro 15-1788, 2 mg/kg i.p., completely but transiently antagonized the antiepileptic action of diazepam, 2 mg/kg i.p. Ro 15-1788, 2 mg/kg, given alone, exhibited no intrinsic activity. At 10-80 mg/kg, it acted as an antiepileptic; this dose-dependent suppressant effect developed slowly over 20-40 min after injection and was never total even at 80 mg/kg. At the highest dose, Ro 15-1788 also had a transient epileptogenic effect immediately following the injection. These results confirm that Ro 15-1788 is not a pure benzodiazepine antagonist but also has partial 'agonist' and 'inverse agonist' properties.

Animals↗
PubMed1984

Enhancement of spike and wave discharges by GABAmimetic drugs in rats with spontaneous petit-mal-like epilepsy.

Certain Wistar rats from our laboratory colony present genetically determined seizures similar to human petit-mal absences. Muscimol, THIP and L-baclofen, agonists of GABA receptors, and gamma-vinyl GABA (GVG), an inhibitor of GABA degradation, enhanced the duration of spontaneous petit-mal-like seizures in a dose-dependent fashion. These findings raise questions as to the role of GABAergic neurotransmission in the occurrence of this type of spontaneous spike and wave discharges.

Action Potentials↗
PubMed1984

Gabaergic modulation of mouse-killing in the rat.

When GABA-potentiating compounds were administered IP to rats with prior experience of mouse-killing behaviour, a reduction of killing was observed with gamma-vinyl GABA (200 and 400 mg/kg) and nipecotic acid amide (400 mg/kg), while no significant effect was noted following injection of dipropylacetate or THIP. The inhibitory effects of gamma-vinyl GABA and nipecotic acid amide were not reversed by subsequent injection of picrotoxin and were associated with sedation as observed in open field and actograph tests. When GABA-potentiating compounds were administered to food-deprived rats exposed for the first time to a mouse (initial elicitation), administration of gamma-vinyl GABA, dipropylacetate, nipecotic acid amide or THIP increased the incidence of mouse-killing behaviour. Conversely, the incidence of mouse-killing under the same conditions was reduced following injections of picrotoxin. These results do not support the hypothesis that the general activation of GABAergic mechanisms inhibits mouse-killing behaviour in rats. On the contrary, data obtained in naive animals suggest that potentiation of these mechanisms actually facilitates the initial elicitation of this behaviour.

Aggression↗
PubMed1984

A model of chronic spontaneous petit mal-like seizures in the rat: comparison with pentylenetetrazol-induced seizures.

Of 100 randomly chosen, adult male Wistar rats in the breeding colony at the Centre de Neurochimie , Strasbourg, 31 presented spontaneous, nonconvulsive epileptic seizures: wave-and-spike discharges, 7-11 cycles/s, 200-600 microV, accompanied by behavioral arrest and myoclony of the vibrissae and of the facial and cervical muscles. Pentylenetetrazol (PTZ) 10 and 20 mg/kg increased the duration and number of seizures by 100-150% in these spontaneously epileptic animals, and caused identical seizures in apparently normal rats. Sodium valproate, diazepam, trimethadione, and ethosuximide suppressed the spontaneous seizures and protected against PTZ-induced seizures in a dose-dependent fashion. Carbamazepine and diphenylhydantoin were inefficacious or aggravative in the two cases. The clinical, EEG, and pharmacological observations suggest that the Wistar rats displaying spontaneous seizures constitute a valid physiological and pharmacological model of petit mal absences, presenting advantages compared to the usual models in which seizures are induced by injected epileptogenic drugs.

Animals↗