Publications (11)0 Total impact
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Article: Spike-wave discharges and sleep-wake states in rats with absence epilepsy
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ABSTRACT: The occurrence of spike-wave discharges was studied in relation to the daily fluctuations of vigilance level in rats. Eight rats of the WAG/Rij strain, an animal model for idiopathic generalized epilepsy of the absence type, which were equipped with cortical EEG and nuchal EMG electrodes, served as subjects. It was found that spike-wave discharges predominantly occur during light slow wave sleep and passive wakefulness. REM sleep, active wakefulness, and deep slow wave sleep are less susceptible to the occurrence of spikewave discharges. Finally, spike-wave discharges tend to prevail in transitional states. A crucial role for the degree of stability of the level of vigilance in the genesis of absence seizures is suggested.Epilepsy Research. -
Article: Dopamine characteristics in different rat genotypes: the relation to absence epilepsy
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ABSTRACT: Dopaminergic neurotransmission has been shown to participate in the control of absence epilepsy. This type of epilepsy, a generalized non-convulsive form, is associated with bursts of bilateral synchronous spike wave discharges (SWDs) recorded in the EEG. In a previous study, it was suggested that two features of the apomorphine-susceptible (APO-SUS) rat genotype, a relatively low dopaminergic reactivity of the nigrostriatal system and relatively high dopaminergic reactivity of the mesolimbic system, contribute to the high incidence of SWDs. Indeed, apomorphine-unsusceptible (APO-UNSUS) rats, characterized by opposite dopaminergic features, show considerably less SWDs than APO-SUS rats. The first goal of the present study was to assess the baseline SWD incidence in four rat genotypes (WAG/Rij, ACI, APO-SUS and APO-UNSUS) in order to replicate previous findings. It was expected that both the APO-SUS and WAG/Rij rats would show a considerably higher SWD incidence in comparison to the APO-UNSUS and ACI rats. For this purpose, rats were registered for a 19 hour period. Assuming that haloperidol decreases dopaminergic transmission in the nigrostriatal system via inhibition of the dopamine receptors and enhances dopaminergic transmission in the mesolimbic system via inhibition of the noradrenergic receptors, it was postulated that haloperidol would enhance the difference in dopaminergic reactivity between both systems in favor of the accumbens. Therefore, the second purpose in the present study was to investigate whether haloperidol (2 mg/kg, IP) could further potentiate SWD incidence when injected in the APO-SUS rats, already characterized by a relatively low dopaminergic reactivity of the nigrostriatal system and relatively high dopaminergic reactivity of the mesolimbic system, in comparison to the APO-UNSUS rat genotype. Finally, the third aim was to study if another epileptic rat genotype, the WAG/Rij, would show similar increases in SWD incidence following an injection with haloperidol as expected for the APO-SUS. First, previous findings were replicated: the value of the hourly number of SWDs decreased in the following order: APO-SUS>WAG/Rij>APO-UNSUS and ACI. Secondly, earlier data were extended by the fact that the APO-SUS responded to a systemic injection of haloperidol with an increase in SWD number and duration, in contrast to the APO-UNSUS rats. The hypothesis that the SWD incidence would be mostly affected by haloperidol in the APO-SUS rats, was confirmed by these findings. It is suggested that haloperidol increases the SWD incidence in APO-SUS rats by enhancing the difference between the dopaminergic reactivity in the nigrostriatal and mesolimbic system. Finally, further research is required to provide evidence in favor of the hypothesis that the relative dominance of the dopaminergic mesolimbic system is smaller in WAG/Rij than in APO-SUS.Neuroscience Research. -
Article: Electrophysiological and pharmacological characteristics of two types of spike-wave discharges in WAG/Rij rats
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ABSTRACT: Rats of the WAG/Rij strain are commonly seen as a genetic model for generalised absence epilepsy in man. Interestingly, generalised absence epilepsy shows, in addition to the fully generalised spike-wave discharges, a second type of spike-wave discharge, which lasts for a shorter time, has a lower frequency, and a lower incidence. The originally described distinction between the two types of spike-wave discharges was mainly based on the shape, polarity and duration of the discharges. In the present study other characteristics such as the spatial and temporal distribution of the spike and wave components of the two discharges and frequency spectra were found to differ between the two types. In addition, a reciprocal regulation of the two types of spike-wave discharges by drugs affecting the dopaminergic system (haloperidol and apomorphine) was observed. The results convincingly demonstrate the difference between the two phenomena and warrant the search for neurobiological mechanisms underlying both types of spike-wave discharges.Brain Research. -
Article: Circadian rhythmicity in absence epilepsy in rats
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ABSTRACT: In order to study putative time of day effects upon the number and mean duration of spike-wave complexes, 19 rats of the WAG/Rij strain were equipped with cortical EEG electrodes. The EEGs were recorded continuously for 48 h. A cosinor analysis was applied to both the data on each subject and the mean scores of all rats. A definite 24 h rhythm was found for the number of spike-wave complexes occurring each hour. The acrophase appeared during the early hours of the dark period, while the minimum was found to take place immediately after the onset of light. A 24 h rhythm was less prominent for the mean duration of the spike-wave complexes. Finally, there were no differences found between the 2 days of the 48 h registration period, suggesting that the number and duration of the spike-wave complexes found on a given day are representative for the following day.Epilepsy Research. -
Article: Cortical and thalamic visual evoked potentials during sleep-wake states and spike-wave discharges in the rat
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ABSTRACT: Flash visual evoked potentials (VEP) were simultaneously recorded from the primary visual cortex and the dorsal lateral geniculate nucleus in freely-moving WAG/Rij rats, to investigate whether the thalamic VEP shows the same state-dependent alterations as the cortical VEP. VEPs obtained during active and passive wakefulness (AW and PW), slow-wave sleep (SWS), REM sleep and during the occurrence of spike-wave discharges (SWD), a specific trait of the genetically epileptic WAG/Rij rat, were compared. The general architecture of the thalamic VEP resembles the cortical VEP, although its polarity is reversed. This facilitated the interpretation of components in terms of underlying neuronal events. The primary excitation peak is differently modulated in cortex and thalamus. Whereas the thalamic component (P30) is not affected by brain-state, the cortical component (N1) shows a strong increase in latency during SWS and SWD. In contrast, the modulation of later components is highly similar for cortex and thalamus. VEPs obtained during AW and REM resemble each other. During SWS and SWD there is a considerable, and during PW a moderate, enlargement of primarily inhibitory components. After-discharges are enhanced during SWS, SWD and REM. No evidence is found for a major impairment of sensory transmission during SWD.Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section. -
Article: Auditory evoked potentials from auditory cortex, medial geniculate nucleus, and inferior colliculus during sleep–wake states and spike-wave discharges in the WAG/Rij rat
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ABSTRACT: Objective: Click auditory evoked potentials (AEP) were simultaneously recorded from the auditory cortex (ACx), the medial geniculate nucleus (MGN), and the inferior colliculus (IC) in the freely moving WAG/Rij rat, to investigate state-dependent changes of the AEP in different anatomical locations along the auditory pathway. Methods: AEPs obtained during active (AW) and passive wakefulness (PW), slow wave sleep (SWS), rapid-eye-movement sleep (REM) and generalized spike-wave discharges (SWD; a specific trait of the WAG/Rij rat, a genetic model for absence epilepsy), were compared. Results: The early components in ACx, MGN and IC were stable throughout the sleep–wake cycle and SWD, apart from a slight increase in the IC during SWD. At all three locations a prominent enlargement of a later component (i.e., N32 in IC, N33 in MGN, and N44 in ACx) was found during SWS and SWD. Conclusions: The early AEP components are not modulated by the normal sleep–wake states, and are not impaired during SWD. A strong state-dependent modulation of a later AEP component occurs at all three anatomical locations investigated. This suggests that apart from the thalamic burst firing mode, additional mechanisms must exist for the enlargement of the AEP during EEG-synchronized states at the prethalamic and cortical level.Brain Research. -
Article: Habituation and sensitization in rat auditory evoked potentials: a single-trial analysis with wavelet denoising
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ABSTRACT: In this work, systematic changes of single-trial auditory evoked potentials elicited in rats were studied. Single-trial evoked potentials were obtained with the help of wavelet denoising, a very recently proposed method that has already been shown to be useful in the analysis of scalp human evoked potentials. For the evoked components in the 13–24-ms range (i.e. P13, N18, P20 and N24), it was possible to identify slow exponential decreases in the peak amplitudes, most likely related to a slow habituation process, while for N18, an initial increase in amplitude was also found. On the contrary, the slower components (N38 and N52) habituated within a few trials, and we therefore propose that they are related to a different functional process. The outcomes of the present study show that wavelet denoising is a useful technique for analyzing evoked potentials in rats at the single-trial level. In fact, in the present study it was possible to obtain more information than the one described in previous related works. This allows the study of other forms of learning processes in rats with the aid of evoked potentials. Finally, the outcomes of this study may have some relevance for the comparison of human and rat evoked potentials.International Journal of Psychophysiology. -
Article: Hippocampal and cortical sensory gating in rats: effects of quinpirole microinjections in nucleus accumbens core and shell
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ABSTRACT: Sensory processing disturbances, as measured in the P50/sensory gating paradigm, have been linked to aberrant auditory information processing and sensory overload in schizophrenic patients. In this paradigm, the response to the second of paired-click stimuli is attenuated by an inhibitory effect of the first stimulus. Sensory gating has been observed in most healthy human subjects and normal laboratory rats. Because mesolimbic dopamine has been implicated in other filtering disturbances such as prepulse inhibition of the acoustic startle response and given the fact that amphetamine and apomorphine have been shown to disrupt gating, this study was performed to investigate the role of mesolimbic dopamine in sensory gating. The dopamine D2 receptor agonist quinpirole (10 μg/0.5 μl) was injected bilaterally in nucleus accumbens core and shell and effects on cortical and hippocampal sensory gating were investigated. Also, effects of the dopamine D2 receptor antagonist haloperidol (0.1 mg/kg, subcutaneously) as pretreatment were studied. First, quinpirole significantly reduced both the amplitude to the first click and gating as measured in the cortex and in the hippocampus. There was a tendency for the quinpirole effects on hippocampal gating to be more pronounced in rats injected in the shell. Secondly, haloperidol did not antagonize effects of quinpirole on hippocampal parameters, whereas haloperidol pretreatment fully antagonized quinpirole effects on cortical parameters.In conclusion, gating can be significantly reduced when a dopamine agonist is specifically targeted at mesolimbic dopamine D2 receptors. However, an important consideration is that the dopaminergic effects in the present study on gating are predominantly mediated by the effects on the amplitude to the first click. This has also been suggested for systemic amphetamine injections in rats and schizophrenic patients. This casts doubt on whether dopamine receptor activation affects the putative inhibitory process between the first and the second stimulus.Neuroscience. -
Article: Sensory gating of auditory evoked potentials in rats: effects of repetitive stimulation and the interstimulus interval
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ABSTRACT: In the P50 gating or conditioning–testing (C–T) paradigm, the P50 response, a small positive midlatency (∼50 ms after stimulus onset) component of the human auditory evoked potential (AEP), is reduced towards the second click (S2) as compared to the response to the first click (S1). This phenomenon is called sensory gating. The putative function of sensory gating is thought to protect subjects from being flooded by irrelevant stimuli.Comparative studies have been done in rats in order to elucidate the underlying neural substrate of sensory gating. However, for a direct comparison of rat and human AEP components, it is imperative for both components to show similar characteristics. The amount of sensory gating in humans is dependent on repetitive stimulation and the interstimulus interval (ISI). In the present study effects of repetitive stimulation (Experiment 1) and various ISIs (Experiment 2) were determined on rat AEP components. The results demonstrate that gating is not limited to a restricted cortical area or a single midlatency component and that repetitive stimulation and ISI affect gating of several rat AEP components. Components such as the vertex P17 and N22 show a decrease in gating within several S1–S2 presentations, mainly due to a decrease in amplitude to S1 (Experiment 1). Gating for vertex components (such as the P17, N22 and N50) is ISI dependent (Experiment 2), but there is no interval in the 200–600 ms range at which optimal gating occurs. The ISI effects on gating are due to an increase of the amplitude to S2. The results have implications for the discussion about the rat homologue of the human P50.Biological Psychology. -
Article: Effects of sertindole on sleep-wake states, electroencephalogram, behavioral patterns, and epileptic activity of rats
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ABSTRACT: In this study we addressed the effects of the 5-HT2 receptor antagonist sertindole in rats. The compound was administered in doses of 0.08, 0.32, and 1.28 mg/kg, whereas a control group received the solvent. The effects of sertindole on sleep-wake states, behavioral patterns, and background electroencephalogram were studied. Following injection of drug or solvent, we recorded the electroencephalogram and electromyogram for two periods of 4 h in the dark period of the light-dark cycle on 2 successive days. On the 1st day sertindole induced a significant increase in deep slow-wave sleep, but only with a dose of 0.32 mg/kg. Furthermore, a decrease in REM sleep in all three drug groups was established. The suppression of REM sleep was still present on the 2nd day. Sertindole also induced a decrease in alternation between behavioral patterns on the 1st day. There were no significant changes in the spectral content of the background electroencephalogram. In a parallel experiment it appeared that sertindole had no main effects on epileptic spike-wave discharges. This was established with a dose of 1.28 mg/kg sertindole in rats with absence seizures. These findings suggest that sertindole, similar to other compounds modulating 5-HT2 receptors, influences sleep-wake states in rats by decreasing REM sleep and mildly increasing deep slow-wave sleep, whereas behavioral variation is slightly diminished, with no effects on the background EEG and almost no effects on spike-wave discharges.Pharmacology Biochemistry and Behavior. -
Article: Antiepileptic and behavioural actions of MK-801 in an animal model of spontaneous absence epilepsy
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ABSTRACT: 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 headwaving 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.Epilepsy Research.
