Biomedical subjects

B W Peeters

Publications and source records attributed to B W Peeters.

30 records · Page 2Linked to original sources

PubMed1992

In vitro and in vivo characterization of the NMDA receptor-linked strychnine-insensitive glycine site.

Modulation of the NMDA receptor by the strychnine-insensitive glycine site was studied both in vitro and in vivo. In vitro the glycinergic stimulation of [3H]MK801 binding was measured in three different rat forebrain membrane preparations. An increased association rate of [3H]MK801 in the presence of glycine was observed. The binding of the radioligand was also enhanced by D-serine, whereas L-serine was less potent. The concentration-effect curves were shifted to the right by the glycine antagonist 7-chlorokynurenic acid (7CKA). In vivo modulation of the N-methyl-D-aspartate (NMDA) receptor was studied using NMDA induced convulsions in 7 day old rats. The NMDA effect was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten,5,10-imine maleate (MK801) and D-(-)-2-amino-5-phosphono-pentanoic acid (AP5). The effect of a submaximal dose of NMDA was dose-dependently potentiated by 1-10 mg/kg D-serine, whereas higher doses of L-serine were needed to obtain a similar effect. 7CKA did not affect NMDA-induced convulsions but reduced the D-serine potentiation of NMDA responses. This study illustrates the ability of the strychnine-insensitive glycine site to modulate the NMDA receptor function both in vitro and in vivo.

2-Amino-5-phosphonovalerate↗

PubMed1991

CNQX, a new non-NMDA receptor antagonist, reduces spike wave discharges in the WAG/Rij rat model of absence epilepsy.

The effects on seizures, EEG and behavior of the non-NMDA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), were studied in the WAG/Rij rat with absence epilepsy. Intracerebroventricular injections (10, 50, and 100 nmol/5 microliters CNQX) showed that CNQX decreases the number of spike wave discharges in a dose-dependent way. Coinjection of CNQX (100 nmol/5 microliters) and AMPA (0.1 pmol/5 microliters), kainic acid (0.01 nmol/5 microliters) or NMDA (50 pmol/5 microliters) attenuated the CNQX response, indicating that CNQX acts on both non-NMDA and NMDA receptors. The observed effects appear to be specific manipulations of the epilepsy not mediated by behavioral changes.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1991

Absence epilepsy and the level of vigilance in rats of the WAG/Rij strain.

In man, a relationship exists between sleep-wake states and absence epilepsy. During wakefulness, spike-wave discharges predominantly occur when the level of vigilance is not high, while during sleep they have a preference to occur during slow-wave sleep. During this latter type of sleep, spike-wave discharges prevail in periods where slow-wave sleep is light. In a series of experiments, the WAG/Rij rat model for absence epilepsy was characterized with respect to the relationships between the level of vigilance, sleep-wake states and the occurrence of spike-wave discharges. In the first experiment, continuous recordings were made for a period of 48 h and a clear circadian rhythm was established for the number of spike-wave discharges. A maximum appeared during the middle of the dark period of the rat, whereas a minimum was detected directly after the onset of the light period, the time period during which deep slow-wave sleep predominates. The relationship of spike-wave discharges with states of vigilance was elaborated in a second study. Spike-wave discharges were mainly found during light slow-wave sleep, during passive wakefulness and in transition phases from sleep to wakefulness. During REM sleep no spike-wave discharges were found. In the last three experiments, the level of alertness was enhanced by various procedures as photostimulation, a learning task and deprivation of REM sleep. In all cases, an increase of alertness decreased the amount of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Diazepam and Ro 15-1788 increase absence epilepsy in WAG/Rij rats chronically exposed to diazepam.

The mechanisms underlying tolerance to benzodiazepines were investigated by injecting diazepam (5 mg/kg) twice daily for 23 days in WAG/Rij rats (an animal model for non-convulsive absence epilepsy). After this the rats received either the agonist, diazepam, or the antagonist, flumazenil (Ro 15-1788). EEG analyses showed that both compounds increased the amount of absence epilepsy-like phenomena. This suggests that repeated administration of diazepam moves the benzodiazepine receptor spectrum towards the inverse agonist end.

Animals↗

PubMed1990

Genetics of absence epilepsy in rats.

All rats of the WAG inbred strain show electrophysiological and behavioral phenomena reminiscent of human absence epilepsy. To study the genetic architecture of this kind of epilepsy, WAG rats were cross bred with inbred ACI rats which show no signs of epilepsy. Number and duration of spike-wave discharges per hour were determined from 24-h recordings of cortical EEG in parental strains and reciprocal F1 hybrids. All hybrids showed spike-wave discharges, indicating complete dominance for occurrence, but different genetic backgrounds were suggested for number and duration of the phenomena. These results imply that more than one gene is involved in absence epilepsy. Some genes determine the occurrence, while others may manipulate the actual number and duration of the epileptic phenomena.

Animals↗

PubMed1990

Involvement of NMDA receptors in non-convulsive epilepsy in WAG/Rij rats.

The involvement of the NMDA receptor in spontaneous non-convulsive epilepsy was studied by intracerebroventricular injections of APH and NMDA in WAG/Rij rats. The WAG/Rij rat strain is recognized as an animal model for human absence epilepsy. EEG registrations showed that APH (5 nmol/5 microliters; 25 nmol/5 microliters; 50 nmol/5 microliters) causes a dose-dependent decrease in the number and mean duration of the spike-wave discharges, while NMDA (50 pmol/5 microliters; 500 pmol/5 microliters; 5 nmol/5 microliters) induces a dose-dependent increase in the number. The effects of NMDA (5 nmol/5 microliters) can be blocked completely by APH (50 nmol/5 microliters). These results suggest an involvement of the NMDA receptor in experimental non-convulsive epilepsy, observed in the WAG/Rij model.

2-Amino-5-phosphonovalerate↗

PubMed1990

Spontaneous occurrence of spike-wave discharges in five inbred strains of rats.

The number and the duration of the cortical registered spike-wave discharges were studied in four inbred strains of rats (G/Cpb, B/Cpb, BN/BiRij, ACI) and compared to those of the WAG/Rij strain. The latter strain is considered to be a model of absence epilepsy. Eight rats of each strain were recorded during a continuous period of 48 hours. An analysis of variance showed significant strain differences in both the number and the mean duration of spike-wave discharges. The value of both parameters increased in the following order: ACI less than BN/BiRij less than B/Cpb less than G/Cpb less than WAG/Rij, whereby the ACI strain was almost free of spike-wave discharges and the WAG/Rij strain showed a considerable number per hour. Since a clear strain difference between the five inbred strains emerged, the investigation of biological and genetic factors underlying these strain differences may provide useful information for absence epilepsy in humans.

Animals↗

PubMed1989

Effects of GABA-ergic agents on spontaneous non-convulsive epilepsy, EEG and behaviour, in the WAG/RIJ inbred strain of rats.

The effects of GABAergic agents on non-convulsive epilepsy were studied by intracerebroventricular injections of muscimol and bicuculline in WAG/Rij rats. The WAG/Rij rat strain is recognized as an animal model for human absence epilepsy. EEG registrations and behavioural observations showed that muscimol dose-dependently increased the non-convulsive absence epilepsy. Besides this, it induced EEG spikes and body twitches. Bicuculline induced spikes and body twitches as well but decreased the non-convulsive epilepsy. All effects of muscimol can be blocked by bicuculline and vice versa, which suggests that the observed effects are genuine GABAA effects. These results implicate that non-convulsive epilepsy can be caused by a GABAergic hyperfunction.

Animals↗

PubMed1989

Absence epilepsy in rats is reduced by deprivation of REM sleep.

Effects of deprivation of REM sleep on spontaneous occurring spike wave complexes in the WAG/Rij rat strain were studied by means of the pendulum and platform technique. During the deprivation period, which lasted three days, variable results were obtained. While a suppression of the total duration of epileptic activity was found for the pendulum deprived animals, no such evident effect was detected in the platform deprived rats. Probably, instrumental effects are responsible for these differential results. On the other hand, subsequent to deprivation, a prolonged reduction of the total duration of spike wave activity was seen in both deprived groups. While it is known that under normal circumstances absences only occur during low levels of arousal and because there is evidence that deprivation of REM sleep has arousal increasing properties, it is suggested that the reduction in epilepsy is caused by an increase of arousal. This result also implies that, at least in the case of absence epilepsy, REM sleep deprivation is not the crucial factor for the epilepsy provoking effect of total sleep deprivation.

Animals↗

PubMed1987

The paw test: a behavioural paradigm for differentiating between classical and atypical neuroleptic drugs.

An often used animal model based on the effects of neuroleptics on spontaneous behaviour is the catalepsy test. However, this test seems to be particularly insensitive to the atypical neuroleptics thioridazine and, especially, clozapine. We have therefore developed an alternative test, the paw test, which measures the ability of drugs to prevent the spontaneous withdrawal of fore- and hindlimbs in rats, and have compared this with the classical catalepsy test. The results show that: 1) the classical neuroleptic drugs haloperidol and chlorpromazine, the atypical neuroleptic drugs clozapine and thioridazine, the potential atypical neuroleptic drugs molindone and SCH 23390, and the potential classical neuroleptic drug metoclopramide are potent in increasing the hindlimb retraction time; 2) the paw test discriminates between classical neuroleptics which are equipotent in prolonging both the forelimb (FRT) and hindlimb retraction time (HRT) an atypical neuroleptics which are much more potent in prolonging HRT than in prolonging FRT; 3) the non-neuroleptic drugs desipramine, diazepam and morphine do not influence the variables measured in the paw test, although morphine does produce catalepsy; 4) Molindone as well as SCH 23390 behave like atypical neuroleptic drugs in the paw test. In comparison with the classical wood block catalepsy test, the paw test is shown to be superior for predicting the profile of the neuroleptics tested. Although more neuroleptics and non-neuroleptics have to be tested to determine whether false positives and false negatives do occur, we feel that the paw test might be an interesting animal model, because the increase in hindlimb retraction time was associated with the antipsychotic potential, whereas the increase in forelimb retraction time was associated with the potential to induce so-called extrapyramidal side effects.

Animals↗

PubMedDate not supplied

Some solvents for antiepileptics have proepileptic potencies in the WAG/Rij rat model for absence epilepsy.

Some solvents for antiepileptics were tested, for 4 consecutive days, in a rat model (the WAG/Rij inbred strain) for absence epilepsy. Electroencephalogram registrations and behavioral observations suggested that both Tween-80 and a mixture of saline/ethanol/propylene glycol caused an increase in the number of epileptic phenomena. This increase was not significant and restricted to injection day 1 with Tween-80 but was significantly present during all 4 injection days with the saline/ethanol/propylene glycol mixture. Furthermore, with this latter solvent the increase became larger during consecutive days. Because of the proepileptic potencies and the differential time effects of these solvents, their usage should be seriously questioned.

Animals↗

PubMedDate not supplied

Antiepileptic and behavioural actions of MK-801 in an animal model of spontaneous absence epilepsy.

The effects of MK-801, a non-competitive antagonist at the NMDA receptor, were studied in an animal model of spontaneous absence epilepsy (the WAG/Rij rat strain). MK-801 was found to reduce the number of spike-wave discharges and their mean duration. It also caused certain behavioural abnormalities, such as headweaving [corrected] and agitation. The antiepileptic effects of MK-801 may be due to the involvement of the NMDA receptor in absence epilepsy. An alternative hypothesis is, however, that MK-801 induces an increase in agitation which in turn reduces the epileptic activity.

Animals↗