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Biomedical subjects

M Vergnes

Publications and source records attributed to M Vergnes.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1985

Diazepam antagonizes GABAmimetics in rats with spontaneous petit mal-like epilepsy.

Wistar rats in our laboratory breeding colony spontaneously present petit mal-like, non-convulsive, epileptic seizures. In these rats, as in other animal petit mal models, GABAmimetics, agonists of GABA-A receptors such as 4, 5, 6, 7 tetrahydroisooxazolo (5,4-c) pyridin-3-ol (THIP), or inhibitors of GABA catabolism such as gamma-vinyl GABA (GVG) or L-cycloserine (CYC), aggravated the seizures. Diazepam not only abolished the spontaneous seizures but also completely blocked the effects of the GABAmimetics, totally suppressing seizures in rats given THIP, GVG or CYC. These findings show that the mode of action of benzodiazepines is not comparable to a non-specific potentiation of GABA transmission, and suggest that the anti-absence effects of the benzodiazepines could depend on interactions with neurotransmitter systems other than GABA.

4-Aminobutyrate Transaminase↗
PubMed1985

Blockade of "antiabsence" activity of sodium valproate by THIP in rats with petit mal-like seizures. Comparison with ethosuximide.

Wistar rats from our laboratory spontaneously present frequent epileptic seizures whose clinical semeiology, EEG signs and pharmacological reactivity resemble absence seizures in humans. In these rats, GABAmimetics such as THIP enhance the duration of seizures in a dose-dependent fashion. In contrast to the action of these drugs, valproate sodium (VPA), which potentiates GABAergic transmission, abolishes the seizures. VPA injected in association with THIP completely loses its therapeutic effects; moreover, VPA potentiates the aggravating effects of THIP. Ethosuximide which does not interact with GABA, was still effective when given in association with THIP. These findings raise questions as to 1. the role of GABAergic neurotransmission in the occurrence of spontaneous petit-mal-like seizures in the rat, and 2. the mode of action of antiepileptics against these seizures.

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

Antiepileptic action of the beta-carboline ZK 91296 in a genetic petit mal model in rats.

The anticonvulsant action of the benzodiazepine (BZ) receptor partial agonist, ethyl 5-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate (ZK 91296) was studied in rats of Wistar origin exhibiting spontaneous bilateral cortical synchronous spike and wave discharges with a symptomatology paralleling that of human petit mal seizures. ZK 91296 1-16 mg/kg i.p.) attenuated the absence seizures without inducing signs of sedation or disorganized EEG patterns at any dose. Diazepam (1-8 mg/kg i.p.) suppressed seizures but also induced sedation and modified EEG background activity in a dose-related manner.

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

Comparative evaluation of anticonvulsant and toxic potencies of valproic acid and 2-en-valproic acid in different animal models of epilepsy.

The anticonvulsant potency of 2-propyl-2-pentenoic acid (2-en-VPA; trans isomer), a major metabolite of the antiepileptic valproic acid (VPA), was evaluated in different animal models of epilepsy and compared with the respective data for VPA. Four models were used: the maximal electroshock seizure (MES) test in mice, the pentylenetetrazol seizure test in mice, gerbils with 'major' (generalized tonic-clonic) seizures in response to specific sensory stimulation, and rats with chronically recurring, spontaneous 'petit mal' seizures. The overall anticonvulsant profile of 2-en-VPA in these models compared favourably with that of VPA. Both drugs were considerably more potent to block seizures in epileptic rats and gerbils than in the traditional MES and pentylenetetrazol mouse models. As regards toxicity, no side-effects were observed with effective doses of 2-en-VPA in rats and gerbils, whereas in the doses necessary to block MES and pentylenetetrazol seizures in mice (200-300 mg/kg i.p.) 2-en-VPA was more sedative than VPA. LD50 values determined for both drugs were comparable. A major difference between 2-en-VPA and VPA was found with respect to embryotoxicity. Single doses of VPA administered to pregnant mice gave rise to significant teratogenic effects (exencephaly, embryolethality , growth retardation), whereas 2-en-VPA was not embryotoxic, even at extremely high doses (600 mg/kg). The data suggest that 2-en-VPA may be a valuable alternative antiepileptic drug.

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↗
PubMed1984

[A genetic form of petit mal absence in Wistar rats].

One-third of the Wistar rats bred in the Centre of Neurochemistry in Strasbourg, France, develop spontaneous epileptic seizures which from their clinical manifestations, pharmacological responses, and electroencephalographic findings are suggestive of Petit Mal absences. These fits are genetically determined since in two lines selected from affected animals they occurred in 90 p. cent of three generations. The selection of a pure strain should assist in the use of this pharmacologic and neurophysiologic model of Petit Mal epilepsy.

Animals↗
PubMed1983

Induction of mouse-killing in the rat by intraventricular injection of a GABA-agonist.

Intracerebroventricular injections of THIP (2.5 and 5.0 micrograms in 5 microliter) facilitated elicitation of mouse-killing in killer rats placed in a non-familiar environment. The same doses induced well organized mouse-killing responses in 60% of non-killer rats. Concomitantly food intake was elicited. Exploratory activity as well as orientation and approach towards any sensory stimulus were also increased. On the contrary, intracerebroventricular injections of bicuculline methiodide (65 and 125 ng in 5 microliters) suppressed aggressive responses in killer rats. The data support the view that GABA receptors are involved in mechanisms which facilitate elicitation of mouse-killing behaviour as well as other positively motivated responses.

Aggression↗