Biomedical subjects

E L van Luijtelaar

Publications and source records attributed to E L van Luijtelaar.

At least 19 recordsLinked to original sources

PubMed2001

Electrophysiological and pharmacological characteristics of two types of spike-wave discharges in WAG/Rij rats.

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.

Action Potentials↗

PubMed2001

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.

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.

Action Potentials↗

PubMed2001

Auditory information processing in rat genotypes with different dopaminergic properties.

RATIONALE: Auditory filtering disturbances, as measured in the sensory gating and prepulse inhibition (PPI) paradigms, have been linked to aberrant auditory information processing and sensory overload in schizophrenic patients. In both paradigms, the response to the second stimulus (S2) is attenuated by an inhibitory effect of the first stimulus (S1). Dopamine (DA) agonists have been found to reduce gating of auditory evoked potentials (AEPs) and PPI in healthy human subjects and in rats. These effects have been linked to DA hyperactivity in the mesolimbic system. A non-invasive approach in studying the role of the DA system in PPI and AEP gating is to compare rat genotypes that are marked by distinct DA systems. OBJECTIVES: Several questions were asked in the present study. Are PPI and AEP gating disturbed in (a) rats that are marked by a relatively high DA reactivity of the mesolimbic system, namely apomorphine-susceptible (APO-SUS) and WAG/Rij rats or in (b) rats that are marked by a relatively high DA activity of the nigrostriatal system, namely apomorphine-unsusceptible (APO-UNSUS) and ACI rats? Moreover, is the particular DA balance (c) between the nigrostriatal and mesolimbic system related to deficits in PPI and AEP gating? METHODS: For this purpose, the above-mentioned four rat genotypes (APO-SUS, APO-UNSUS, ACI and WAG/Rij) that vary in DA balance between both systems, were compared in the AEP gating paradigm. PPI was only measured in the ACI and WAG/Rij rats, since it has already been shown in a previous study that APO-SUS rats show diminished PPI as compared to rats of the APO-UNSUS genotype. RESULTS: AEP gating of the vertex N50 was significantly reduced in WAG/Rij rats as compared to the remaining three rat genotypes (APO-SUS, APO-UNSUS and ACI). No PPI deficits were found in the ACI and WAG/Rij rats, although ACI rats had a significantly higher basal startle amplitude. CONCLUSIONS: The PPI deficit in APO-SUS and not in the other genotypes, suggests that especially a relatively high DA reactivity of the mesolimbic system, together with a relatively low activity of the nigrostriatal system, contributes to this deficit. In contrast, the N50 gating deficit in WAG/Rij rats and not in the other genotypes suggests that a relatively high DA activity of the nigrostriatal system together with a relatively high DA reactivity of the mesolimbic system is necessary for the presence of a N50 gating deficit. On the basis of these results we have concluded that both auditory filtering processes are differently regulated by DA in the nigrostriatal and mesolimbic systems.

Acoustic Stimulation↗

PubMed2001

PTZ-induced seizures in rats: effects of age and strain.

The susceptibility to pentylenetetrazol (PTZ)-induced seizures during postnatal ontogeny [postnatal day (PN) 10-220] was investigated in two rat strains. The WAG/Rij strain, genetically prone for developing generalized absence epilepsy, and Wistar rats were tested and compared at PN 10, 26, 30, 70, 90, 125, and 220 on the PTZ-convulsive threshold. A subconvulsive dose of 25-mg/kg PTZ was administered every 15 min, and the occurrence of clonic and tonic-clonic seizures was scored. The 10-day-old pups were quite sensitive to PTZ and showed mainly clonic seizures. The highest threshold and latency of PTZ-induced clonic and tonic-clonic convulsions were observed at PN 26 in both strains. From that age onwards, the seizure threshold significantly decreased and reached a minimum at PN 220. Between strain comparisons showed that WAG/Rij rats have a lower tonic-clonic seizure threshold than Wistar rats. The data indicate that changes in susceptibility first quickly decreases until PN 26-30 and then tend to monotonically increase with age, and that genetically prone nonconvulsive WAG/Rij rats are more vulnerable to convulsive seizures induced by PTZ than Wistar rats.

Aging↗

PubMed2001

Sensory gating of auditory evoked potentials in rats: effects of repetitive stimulation and the interstimulus interval.

In the P50 gating or conditioning-testing (C-T) paradigm, the P50 response, a small positive midlatency ( approximately 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.

Animals↗

PubMed2001

Hippocampal and cortical sensory gating in rats: effects of quinpirole microinjections in nucleus accumbens core and shell.

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 microg/0.5 microl) 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.

Acoustic Stimulation↗

PubMed2001

Dopamine characteristics in rat genotypes with distinct susceptibility to epileptic activity: apomorphine-induced stereotyped gnawing and novelty/amphetamine-induced locomotor stimulation.

Rat genotypes differ in their susceptibility to spontaneously occurring spike-wave discharges and in their dopaminergic properties. In a previous study, it was found that spike-wave discharge incidence decreased in the following order in four rat genotypes during baseline and following injection with the dopamine antagonist haloperidol: apomorphine-susceptible (APO-SUS) > WAG/Rij > apomorphine-unsusceptible (APO-UNSUS) and ACI rats. The question in the present study was to what extent certain dopaminergic properties are pathognomonic for epileptic rats. Therefore, behavioral responses were assessed in order to investigate the dopaminergic properties in the four rat genotypes. Apomorphine-induced gnawing data imply that the dopamine activity of the nigrostriatal system in the WAG/Rij rats is higher than in APO-SUS but lower than in the ACI and APO-UNSUS rats. Furthermore, in previous studies APO-SUS have been shown to have a higher novelty/amphetamine-induced locomotion, indicative of a higher dopamine reactivity of the mesolimbic system as compared to APO-UNSUS rats. Results from the present study showed that WAG/Rij rats have a higher locomotor responsiveness to novelty/amphetamine, indicating a higher dopamine reactivity of the mesolimbic system in comparison to the ACI rats. It is suggested that the functional dopaminergic mesolimbic dominance is an important factor in the susceptibility to show spontaneously occurring spike-wave discharges.

Amphetamine↗

PubMed2000

Dopamine characteristics in different rat genotypes: the relation to absence epilepsy.

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.

Action Potentials↗

PubMed2000

Cognitive functioning after whiplash injury: a meta-analysis.

Complaints on cognitive functioning are often reported in patients suffering from whiplash syndrome, although objective neuropsychological test results do not always support these. In addition, radiological abnormalities and anatomical lesions are found only in a minority of these patients. This has led to a controversy about its existence in the literature. In this systematic review, the results of 22 neuropsychological studies on whiplash were quantitatively analyzed, focusing on working memory, attention, immediate and delayed recall, visuomotor tracking, and cognitive flexibility. Our findings suggest that a consistent overall pattern of cognitive dysfunction can be demonstrated after whiplash injury through neuropsychological testing, both compared to healthy and to asymptomatic controls. Six months after the accident, improvement is found in working memory, attention, immediate recall, and visuomotor tracking. The results are discussed in the light of recent findings on the effect of cerebral dysfunction, malingering, pain-related factors, and the role of coping strategies and posttraumatic stress on neuropsychological test performance.

Brain Injury, Chronic↗

PubMed1999

Differential effects of ketamine on gating of auditory evoked potentials and prepulse inhibition in rats.

Schizophrenic patients suffer from deficits in information processing. Patients show both a decrease in P50 gating [assessed in the conditioning-testing (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substrate. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these information processing paradigms in animals in order to investigate the effects of neurotransmitter manipulations in the brain. In order to validate the animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/kg, i.p.) was administered. Gating of an AEP component was changed due to injection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, i.p.) was investigated to assess its effects in the two gating paradigms. It was found that ketamine (10 mg/kg) did not affect gating as measured with components of the AEP. However, ketamine (10 mg/kg) disrupted PPI of the startle response to the extent that prepulse facilitation occurred. Firstly, it is concluded that AEP gating was disrupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T paradigm reflect distinct inhibitory sensory processes, since both paradigms are differentially influenced by ketamine.

Animals↗

PubMed1998

Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis.

Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best defined electrophysiological abnormalities are the changes in event-related potentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less familiar are the changes observed in the electroencephalogram of CEAE-affected animals, which are also encountered in the human equivalent, MS. In the present experiment we evaluated the therapeutic value of a neurotrophic peptide treatment [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH, an ACTH4-9 analogue] and its effect on the delayed flash visual evoked potentials (VEP) and power spectra of the electroencephalogram, during a 17-week follow-up of CEAE. CEAE animals treated with the neurotrophic peptide were protected against the development of neurological symptoms during the course of the demyelinating syndrome. VEPs of animals suffering from CEAE showed a delay of the latencies of the late components which was significantly counteracted by peptide treatment. The peak-to-peak amplitude of the VEP afterdischarge recorded from CEAE animals was significantly increased during the course of CEAE and correlated closely with the progression of the myelinopathy. Furthermore, CEAE animals showed an increase of electroencephalogram (EEG) beta activity of up to 500% as compared with the age-matched control group. This increase in beta power mainly consisted of a prevailing 20-21 Hz peak, a frequency that normally is not dominant in control EEG recordings of the rat during passive wakefulness. All these electrophysiological phenomena were absent in ACTH4-9 analogue-treated animals. The present findings underscore the potential importance of a neurotrophic peptide treatment in the pharmacotherapy of central demyelinating syndromes, and possibly of MS.

Adrenocorticotropic Hormone↗

PubMed1998

The whiplash syndrome: a psychophysiological and neuropsychological study towards attention.

Whiplash patients often have physical, psychosomatic and cognitive complaints, although clear neurological and neuropsychological signs of damage are absent. However, in some studies a functional loss of attention was found. In order to compare attentional dysfunctions in whiplash patients with age-matched controls, attention was measured neuropsychologically with the aid of the PASAT, and psychophysiologically with the aid of the prepulse inhibition paradigm. In addition, the reactivity for intense acoustic stimulation was investigated. The POMS and the SCL-90 were used to evaluate psychological and somatic signs. The results showed that whiplash patients (n=24) had lower scores on the PASAT and higher scores on the questionnaires compared to healthy controls (n=21). However, no group differences could be determined on the psychophysiological variables. Furthermore, the PASAT and prepulse inhibition data did not correlate. The lower PASAT scores indicate that whiplash patients seem to have deteriorated divided attention, but an attention deficit as measured with the prepulse inhibition paradigm is not disclosed. Finally, there were no signs of a heightened reactivity of the auditory system, which casts doubts on a presumed heightened sensitivity for sound in whiplash patients.

Acoustic Stimulation↗

PubMed1998

Differential effects of non-REM and REM sleep on sensory gating in rats.

Sensory gating in rats can be measured with a double click paradigm. The diminished response towards the second click is a physiological manifestation of reduced sensory input. This physiological process seems to be disturbed in human psychoses. It is thought that gating, as measured with this paradigm, is a preattentive, involuntary phenomenon which is not modulated by attention. If this is indeed the case, than it is hypothesized that gating should not be modulated by non-REM sleep. In the present experiment pairs of clicks (500 ms interval) were presented during wakefulness, non-REM as well as REM sleep and cortical auditory evoked potentials (AEP's) were recorded in chronically implanted rats. Rather similar AEP's were found after the first and second stimulus. However, the amplitudes of the various components of the second AEP were smaller than those of the first AEP, suggesting a gated response. This was the case during all three levels of vigilance. The amplitudes of both AEP's showed the more often reported changes in amplitude during sleep and REM sleep. Clear differences were seen in gating: compared to wakefulness a decrease in gating was found during REM sleep while gating was unchanged during non-REM sleep. The latter outcome seems to confirm that gating in rats is indeed a preattentive process. Finally, results were discussed in terms of neuronal properties of thalamic relay cells and it is suggested that firing properties of thalamic relay cells are not involved in this type of sensory gating.

Acoustic Stimulation↗

PubMed1997

Event-related potentials in a passive and active auditory condition: effects of diazepam and buspirone on slow wave positivity.

The effects of single, oral doses of diazepam (10 mg), buspirone (10 mg) and placebo on auditory event-related potentials were assessed in healthy volunteers. Subjects received two series of auditory stimuli: a series of identical stimuli presented in a neutral, passive condition and a series of identical standard tones (P = 0.8), but now intermixed with target tones (P = 0.2), in an active, oddball condition. The analysis focused on the average value of the potential in two different phases, from 250 till 574 ms post-stimulus (including P300) and from 576 till 900 ms post-stimulus (including late slow wave positivity). Event-related potentials for the standards of the oddball task were compared with the potentials of the same stimuli presented in the neutral condition. In addition, the classical comparison between the target and the standard in the oddball task was made. The first comparison was designed to isolate any effect of a change in the level of vigilance and attention due to involvement in the oddball task. This effect was evident as an increase in positivity that was smaller in the diazepam condition. The second comparison was designed to isolate the distinctive processing associated with task-relevant stimuli. This revealed that the P300 was reduced in the 250-574 ms window in the diazepam group. Both results suggest that cognitive processing of relevant stimuli is reduced by diazepam. Presumably, this is associated with the sedative effects of this drug. Consistent with this interpretation, subjects under the influence of diazepam made more omissions in the detection of targets in the oddball condition and had longer reaction times. In contrast to diazepam, the anxiolytic buspirone did not appear to have measurable effects on cognition.

Adult↗

PubMed1997

Influence of diazepam and buspirone on human heart rate and the evoked cardiac response under varying cognitive load.

The influence of two anxiolytics on basal heart rate and on the evoked cardiac response elicited by auditory stimuli, was studied in humans. Diazepam (Valium) (7.5 mg) and buspirone (Buspar) (7.5 mg), which differ in their psycho-pharmacological profiles, were used. Prestimulus vigilance and cognitive load were manipulated by instructions allowing the subjects to ignore the stimuli, or requiring them to count the tones. Drug effects were obtained in subjective alertness, basal heart rate level, and the evoked cardiac response. Diazepam reduced subjective alertness, while buspirone did not. Diazepam apparently increased heart rate levels relative to placebo, in contrast to buspirone, which produced an apparent decrease in heart rate. These drug-induced prestimulus heart rate level effects were associated with differential decelerations immediately following stimulus onset and appear to reflect differences in prestimulus vigilance. Opposite effects of the drugs were also observed in the second, acceleratory, component of the of the evoked cardiac response, and these were found to be independent of the prestimulus drug effects. Compared with placebo, buspirone appeared to enhance the acceleratory component in the count condition, while diazepam led to an apparent reduction of this component. Enhancement of this acceleration after buspirone may reflect an increase in cognitive effort directed to the performance of task-relevant behaviour, while the reduction of this component after diazepam can be regarded as a cognitive-motivational neutralisation of signal value. The differential effects of the two anxiolytics support the separation of the evoked cardiac response into different components and may also have implications for the clinical use of the drugs.

Acoustic Stimulation↗

PubMed1997

Spike-wave discharges and sleep spindles in rats.

Sleep spindles and spike-wave discharges are thought to originate from the same thalamic pacemaker. In the present work it is investigated whether sleep spindles and spike-wave discharges are also sensitive for the same drugs. Adult male WAG/Rij rats were chronically implanted with frontal and occipital EEG electrode pairs. Rats were intraperitoneally injected with clonidine (0.00625 mg/kg), phenobarbital (20 mg/kg), flunitrazepam (0.188 mg/kg). Frontal and occipital sleep spindles and mainly frontal spike-wave discharges were seen in the electroencephalogram. Phenobarbital and flunitrazepam reduced the number of spike-wave discharges and enhanced frontal sleep spindles, while clonidine facilitated spike-wave discharges and reduced frontal sleep spindles. The results of these three drugs indicate a reciprocal relationship between the number of frontal sleep spindles and the number of spike-wave discharges. Only clonidine facilitated occipital sleep spindles without an effect on spike-wave discharges. It can be concluded that frontal and occipital sleep spindles have a different pharmacological profile. Furthermore, the inverse relationship between frontal sleep spindles and spike-wave discharges may suggest that sleep spindles and spike-wave discharges are controlled by a single controlling system. However, in order to explain the clonidine data on occipital sleep spindles another factor must be incorporated in properties of the mechanism(s) involved in EEG oscillations.

Adrenergic alpha-Agonists↗

PubMed1997

Effects of benzodiazepines, sleep and sleep deprivation on vigilance and memory.

Anterograde amnesia is one of the troublesome adverse effects of the benzodiazepines, especially when they are used as tranquillizers. Interestingly, benzodiazepines also produce retrograde facilitation. In this review, a unifying hypothesis concerning both the cognitive enhancement and the cognitive decrement is discussed: the decrease in vigilance or sedative-hypnotic properties of the benzodiazepines induces a superficial type of encoding and consolidation. This is expressed in anterograde amnesia. The shallower encoding also causes less retrograde interference and retrograde facilitation is the result. In this way also the positive effect of sleep on memory is explained. In a series of experiments, this hypothesis was investigated. Anterograde amnesia and retrograde facilitation was demonstrated after benzodiazepine intake in healthy, volunteers. It was striking that amnestic effects and retrograde facilitation were most prominent when memory was tested one week after drug intake. A decrease in vigilance was also obtained by sleep deprivation and an increase by the gavage of the central stimulant methylphenidate. The latter vigilance increasing drug did not change memory aspects. Also memory effects were hardly present in sleep deprived subjects with low levels of vigilance and the performance on memory tests were not changed. This jeopardizes the vigilance hypothesis of the memory effects of the benzodiazepines. However, amnesia under the influence of benzodiazepines was less for semantic related words than for unrelated words. This suggests that information might be stored without appropriate contextual cues. Only under special circumstances this information can be retrieved. It is further speculated that this storage costs less efforts leading to less retrograde interference and consequently retrograde facilitation.

Amnesia↗

PubMed1996

Effects of acute and chronic cocaine administration on EEG and behaviour in intact and castrated male and intact and ovariectomized female rats.

Intact and gonadectomized male and female WAG/ Rij rats were used to study the effects of gender and gonadal hormones on the development of sensitization and tolerance to cocaine-induced changes in EEG and behaviour. The four groups of WAG/Rij rats differed in the number of spontaneously occurring spike-wave discharges: ovariectomy decreased and castration increased the number of spike-wave discharges. This confirms that testosterone has antiabsence effects and that female gonadal hormones may promote the occurrence of spike-wave discharges. Cocaine [10 and 20 mg/kg, intraperitoneally (IP)] was administered before and after chronic cocaine administration (9 days, one daily injection with 10 mg/kg) and EEG and behaviour were monitored. Cocaine strongly suppressed the occurrence of spike-wave discharges before and after chronic administration in all four groups, although the decrease was less in the intact males. Sensitization or tolerance induced by cocaine on EEG could not be established. Acute cocaine administration eliminated explorative, automatic, and passive behaviour, whereas various stereotypical activities such as uncoordinated head and body movements and head swaying emerged. Differences between groups were observed as intact males were less likely than subjects in the three other groups to engage in intense stereotyped behaviour. These data suggest that testosterone inhibits EEG and behavioural effects of acute cocaine administration. All four groups displayed less head swaying and more uncoordinated head and body movements after chronic cocaine administration, suggesting that behavioural sensitization had occurred. Differences between the four groups had faded away. Although pharmacokinetic differences in levels of cocaine and benzoylecgonine between the four groups were found, they could not easily be related to the behavioural differences between groups.

Animals↗