R. Dirksen

Correlation dimension of the human electroencephalogram corresponds with cognitive load

This study aimed at assessing the effects of cognitive activity and mental task load on the correlation dimension of the human electroencephalogram (EEG). Three experimental conditions were created: a baseline condition and two cognitive task conditions, a calculation task and a time estimation task. The calculation task was supposed to induce a higher mental load than the time estimation task, which is regarded as a less complex one. This was verified by a subjective rating scale. All conditions differed significantly in subjective estimated task load. The correlation dimension appeared to be higher in both task conditions compared to the baseline condition. A comparison of the two tasks indicated that the difference in correlation dimension between calculation and time estimation was also significant, with the highest value for calculation. It is concluded that cognitive and mental activity is associated with a higher correlation dimension in the EEG. This implies that the correlation dimension is a sensitive parameter in the analysis of electrical brain activity.

Selective serotonin reuptake inhibitors may enhance responses to noxious stimulation.

The acute effects of various doses of two selective serotonin reuptake inhibitors (fluoxetine and fluvoxamine) on thermal and electrical stimulation-induced pain were investigated in drug-naive Wistar rats. The hot-plate and the tail-flick test and the noxious-induced withdrawal test were used. The two drugs had no effects on heat-induced pain behavior. However, the two compounds enhanced the motor responses induced by noxious electrical stimulation. These data contrast to what is generally found for tricyclic antidepressants and suggest a modality specific pain system. Cardiac and blood pressure were also found to change, but these changes were not correlated to changes in nociception. Taken together, the data suggest that the acutely administered selective serotonin reuptake inhibitors may exacerbate an acute type of pain.

Contractures in skeletal muscle of malignant hyperthermia susceptible patients after in vitro exposure to sevoflurane

Background: Sevoflurane, a potent inhalational anaesthetic agent that is structurally similar to halothane, has some favourable characteristics, but may also be able to trigger malignant hyperthermia (MH) in susceptible patients. The diagnosis of malignant hyperthermia susceptibility relies on the in vitro contracture test on skeletal muscle. The present study was undertaken to investigate whether exposure to sevoflurane of muscles of malignant hyperthermia susceptible (MHS) patients would also cause an abnormal contracture.

A molecular model for the synergic interaction between γ-aminobutyric acid and general anaesthetics

Within the context of the discussion about rational polytherapy, we determined the effects of four anaesthetics on the binding of [3H]t-butylbicycloorthobenzoate ([3H]TBOB) to the GABA(A) receptor complex in the presence of several concentrations of GABA (gamma-aminobutyric acid), in order to build a molecular model that can describe and quantify the interactions between the compounds. The empirical isobole method revealed that GABA and the anaesthetics acted synergically in displacing [3H]TBOB. This synergy could be described by a simple molecular model in which both GABA and the anaesthetics displaced [3H]TBOB allosterically and in which GABA allosterically enhanced the binding of the anaesthetics. To get information about the interaction between GABA and anaesthetics, we used [3H]TBOB as a tracer ligand. The model indicated that GABA enhanced the affinity of thiopental 3.0-fold, propofol 5.0-fold, the neuroactive steroids Org 20599 3.5-fold and Org 20549 13-fold. Insight into the molecular mechanism and strength of these interactions can help clinicians to choose therapeutically optimal drug and dose combinations: a step towards rational polytherapy.

Time course of chronic diazepam effects on the auditory evoked potential of the rat

The time course of chronic diazepam effects on auditory evoked potentials was studied in rats. Auditory evoked potentials were elicited by background and target tones in a passive oddball paradigm. Diazepam was administered by slow release implants to establish constant blood concentrations. Recordings were made during 21 days of treatment and 9 days after treatment ceased. Diazepam increased the amplitude of the P40 component and decreased the amplitude of the P72-P102 components elicited by background tones. Diazepam increased the amplitude of the P40-P48 component and decreased that of the N58 component elicited by target tones. These effects remained constant during treatment. Diazepam further decreased the amplitude of the P102 component elicited by target tones. This effect became more distinct over time. No group differences were found 9 days after treatment. The constant drug effects on middle-latency components (P40-P48) might reflect diazepam-induced changes in sensory information processing. The decreased long-latency component (P102) might reflect a diminished attention to, or discrimination of, target tones. The time course of this effect might reflect diazepam-enhanced habituation.

Pancuronium masks the prejunctional muscarinic autoreceptor in guinea pig tracheal smooth muscle.

The effect of pancuronium pretreatment on the function of the prejunctional muscarinic receptor in guinea-pig trachea was studied by using electrical field stimulation (EFS). The effects of cumulative doses of the muscarinic M2 receptor antagonist gallamine were investigated in tracheal smooth muscle strips from guinea-pigs after addition of pancuronium in vitro and in strips from guinea-pigs which had been pretreated with doses of pancuronium that caused 100% neuromuscular blockade. The results of both types of experiments were compared to those of control groups of the same size. In all strips a dose response curve with cumulative doses of methacholine was made before EFS was switched on. No differences were found between the mean pD2 value and slope of the concentration-response curves of untreated guinea-pigs and animals treated with anaesthetics and pancuronium. The animals showed variable responses to pancuronium. The bath concentration of pancuronium which decreased the EFS-induced contraction to half the original value varied between 14-61 microM. The intravenous dose necessary to paralyze the muscles, varied among the different guinea-pigs from 0.017-0.085 mg.kg-1. The EFS-induced contraction for the concentration range of gallamine 0.32 microM-0.32 mM was found to differ significantly between the strips treated with pancuronium in the organ bath and their control group. For the guinea-pigs anaesthetized and pretreated with pancuronium a significant difference with control was observed at gallamine concentrations ranging from 0.032-0.32 mM. These results show that pancuronium, added to the organ bath as well as administered intravenously to the guinea-pig, masked the inhibitory muscarinic receptor.

Diazepam biphasically modulates [3H]TBOB binding to the convulsant site of the GABAA receptor complex

Interactions of GABA, bicuculline methochloride and diazepam with [3H]TBOB binding to rat brain membranes were evaluated in vitro. GABA displaced [3H]TBOB binding with and IC50 of 4 microM and a slope factor near unity. The competitive GABA antagonist bicuculline methochloride shifted the displacement curve of GABA parallelly to the right, indicating that the interaction of GABA with [3H]TBOB binding is of an allosteric nature. In the presence of GABA, diazepam displaced the binding of [3H]TBOB according to a two-site model: a high affinity site with an IC50 of about 50 nM and a lower affinity site with an IC50 of about 30 microM. Bicuculline methochloride abolished the nanomolar displacement by diazepam and increased the micromolar IC50 value. These results indicate that the interaction of the high affinity diazepam site with the [3H]TBOB binding site is totally GABA dependent and that the low affinity effect of diazepam on [3H]TBOB binding is at least partially GABA dependent. It is likely that the low affinity potency of diazepam to displace [3H]TBOB binding has physiological relevance.

Responses to propofol in relation to GABA functionality of discrete parts of the brain of rats

Genetically-determined regional differences in the GABA-ergic make-up of the brain exist in two lines of Wistar rats viz apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) Wistar rats, Propofol is a GABA-mimetic general anesthetic. This study compared the responses to propofol in APO-SUS and APO-UNSUS rats. Propofol induced a higher incidence of involuntary muscular contractions and oral movements, but a lower incidence of grooming, in APO-SUS rats than in APO-UNSUS rats. Reflex inhibition and narcosis, being defined as the behavior marked by both full absence of purposeful movements and by complete loss of righting reflexes, after propofol did not differ between the two lines. APO-SUS rats had less variation of the heart rates and greater variations of diastolic arterial pressures in response to electrical stimulation than the APO-UNSUS rats, and these variations were reduced by increasing doses of propofol. Arterial pressures in APO-SUS rats were higher than in APO-UNSUS rats. Propofol caused a biphasic change in intra-arterial pressures and had the greatest effect in APO-SUS rats. Differences in cerebral GABA transmission, especially in the striato-nigro-collicular pathway, did not give rise to differences in the effect of propofol on narcosis and hindlimb withdrawal reflex. In contrast, these differences in GABA transmission were accompanied by line-specific differences in effect of propofol on certain behavioral and cardiovascular parameters.

Influence of the power-spectrum of the pre-stimulus EEG on the consecutive Auditory Evoked Potential in rats.

Evoked Potentials (EPs) are responses that appear in the EEG due to external stimulation. Findings indicate that changes in EPs can be related to changes in frequencies of the pre-stimulus EEG. Auditory EPs of rats (n=8) were measured in reaction to tone-pip stimuli (90 dB, 10.2 kHz, ISI 2s, n=1500). Trials were ranked according to the percentage of delta (1-4 Hz), theta (5-8), alpha (9-12) or beta power (13-30 Hz) in the pre-stimulus EEG. Consecutive AEPs were computed. An increase in beta and a decrease in delta resulted both in an increase in the N60 and P70 component and a decrease in the P150-200 component. These beta and delta changes have been associated with changes in arousal. The increased N60 and P70 components with increases in beta might reflect increased attention due to an increase in arousal. We found that an increase in delta activity, leads to an increase of the late-latency P150-200 component, possibly due to an increased synchronization in the EEG.

Irradiation and responsiveness to pain stimuli in rats

This study evaluates whether irradiation inhibits responses to pain in an animal model. We found that irradiation with doses of 10 Gy, 15 Gy and 17.5 Gy of the lumbar enlargement of the spinal cord inhibits the behavioural responses to the stimulus of the hot-plate. These doses were otherwise without effects. This data is discussed in view of the effects of irradiation of living cells, and we propose that a modification of pain signal processing is accomplished. Similar considerations apply to the human condition.