[Activated amino acid receptors in normal and pathologic brain function].
Explore the source record for details and available documents.
Basal Ganglia Diseases↗
Biomedical subjects
U Tacke
Publications and source records attributed to U Tacke.
Mania induced by biochemical imbalance.
Explore the source record for details and available documents.
Bipolar Disorder↗
Inhibition of sound-induced convulsions by metoprine in the audiogenic seizure susceptible rat.
Metoprine which increases brain histamine by blocking its methylation, was recently demonstrated to inhibit electrically induced tonic convulsions in rats. Its effect was now tested on audiogenic convulsions in genetically audiogenic seizure sensitive rats. Metoprine (20 mg/kg, i.p.) reduced the severity of seizures significantly 4 and 28 h after drug administration. Also the duration of convulsions was significantly decreased. These results agree with an involvement of histaminergic neurons in convulsive phenomena perhaps as a part of an anticonvulsive inhibitory transmitter system.
Acoustic Stimulation↗
Heat stress and neuroleptic drugs.
Explore the source record for details and available documents.
Adult↗
"In vivo" visualization by positron emission tomography of the progressive striatal dopamine receptor damage occurring in MPTP-intoxicated non-human primates.
Intravenous administration of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) leads to the progressive development of a model of Parkinson's disease in the primate. The development of damage occurring in the striatal area during MPTP-treatment was followed "in vivo" in a baboon by positron emission tomography (PET). Spiperone labelled with a positron emitter 76Br (76Br-BSP) was used for the quantitative "in vivo" imaging of D2 dopamine receptors. The decrease in the striatal binding of 76Br-BSP measured "in vivo", after three series of MPTP injections, paralleled the increase in the severity of behavioral symptoms seen immediately after administration of the neurotoxin. At the end of the MPTP-treatment when neurological symptoms were the most important, a 36% decrease in the 76Br-BSP specific binding was measured. Between the series of MPTP injections a partial recovery in the quantitative measurement of the 76Br-BSP specific binding occurring in the striatum was well correlated with the disappearance of the neurological syndrome. Post-mortem histological and biochemical studies in nigro-striatal anatomical structures of MPTP-intoxicated primates compared with control animals showed a 80% loss of neuronal cell bodies in the substantia nigra compacta and a 42% decrease in the density (Bmax) of D2 receptors (in vitro 3H-spiperone binding). All these results showed that the use of PET and 76Br-BSP allow to follow in a noninvasive way both the degenerative processes and the subsequent partial recovery which occur in dopaminergic striatal receptor function during MPTP-treatment.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Is histamine an anticonvulsive inhibitory transmitter?
This study was done to investigate the possible role of histaminergic systems in electroshock seizures. Brain histamine concentrations in rats were elevated by metoprine (i.p.), an inhibitor of histamine-N-methyltransferase. Animals were tested for their response to maximal electroshock (MES) at different times after the injection. Metoprine raised brain histamine concentrations and inhibited maximal hindleg extension after MES in a dose-dependent manner. Sensitivity to seizures correlated inversely with histamine concentrations. These results suggest that histaminergic neurones are involved in mechanisms which inhibit generalizations of epileptic discharges in the brain.
Animals↗
Sounds with harmonic spectra are more effective than pure tones in inducing audiogenic seizure in rats.
Twenty rats of an audiogenic seizure (AGS)-susceptible stock were exposed to four different sound stimuli and seizure severity and seizure-latency were registered. Two sounds with harmonic spectra, one pure tone and band noise were used. The harmonic spectra were found to be significantly (P less than 0.005) more effective than the other stimuli in inducing AGS when seizure-latency was taken as a parameter. Connections from the auditory pathway to the reticular formation seem to be of importance in the triggering of these seizures. AGS-susceptible rats may offer a useful tool for experimental hearing research.
Acoustic Stimulation↗
Seizure thresholds and their postictal changes in audiogenic seizure (AGS)-susceptible rats.
The convulsive thresholds for bicuculline and electroshock seizures were studied in audiogenic seizure (AGS)-susceptible and control rats. Electroshock seizure thresholds, determined as the amperage necessary to cause tonic extension of the hindlegs in 50% of the rats (CC50 = convulsive current fifty) were markedly lowered in rats of two stocks, bred for AGS susceptibility. During the clonic phase of electroshock seizure the bicuculline threshold was slightly lowered but started to rise after the convulsion had ceased. After 5 min, the threshold was significantly elevated and the maximal increase was reached in 15 min. In control rats the level normalized curvilinearly within an hour, but in AGS rats it decreased more slowly and was still elevated after 90 min. After an audiogenic seizure, the threshold for bicuculline-induced seizures in AGS rats also rose significantly but declined rapidly after having reached a maximum at 15 min. This rise in seizure threshold for bicuculline might indicate a postictal change in GABAergic transmission.
Acoustic Stimulation↗
Cortical spike wave discharges during audiogenic convulsions in rats.
Audiogenic seizure-susceptible rats show high-amplitude spikes and waves in the electrocorticogram during the tonic phase of a maximal audiogenic convulsion. This observation establishes the validity of this seizure type as an animal model for human generalized epilepsy.
Acoustic Stimulation↗
The effect of changes in sound pressure level and frequency on the seizure response of audiogenic seizure susceptible rats.
An apparatus for pure tone stimulation of audiogenic seizure (AGS)-susceptible rats is described, and the effect of change in sound pressure level and frequency on AGS response in Uaz:AGS (SD) rats is shown. By use of pure tone stimulation, the prevalence of AGS response in rats of this strain, which have been bred for seizure-susceptibility, is 77%. With increasing frequency, the intensity-response curves show a shift to lower sound pressure levels, the ED50 for 20 kHz (83.8 dB) being significantly lower than the ED50 for 5 (110.5 dB) and 10 kHz (97.5 dB). Repeated exposure to seizure-inducing sound at weekly intervals leads to more severe seizures in individual rats. This should be taken into consideration as one possible confounding factor when using this method for assaying the efficacy of anticonvulsant drugs.
Acoustic Stimulation↗
The effect of clonidine and yohimbine on audiogenic seizures (AGS) in rats.
Clonidine in high doses (0.5,1.0 mg/kg) significantly increased the latency for audiogenic seizures (AGS) in rats and reduced seizure severity. At a dose (0.05 mg/kg) which acts more specifically on presynaptic alpha 2-receptors, clonidine did not affect seizure latency, but showed a slight proconvulsant action. Yohimbine tended to decrease seizure-latency at all doses, but statistical significance (p less than 0.05) was only reached at 10 mg/kg. Smaller doses of yohimbine (0.5 and 1.0 mg/kg) showed a proconvulsant effect, while a high dose (10 mg/kg) markedly reduced the severity of AGS. The effect of clonidine on seizure-latency was only antagonized by high-dose yohimbine (10 mg/kg), the combination of these drugs being of marked anticonvulsant efficacy. From these results it can be concluded that the anticonvulsant effect of clonidine does not seem to be mediated through presynaptic alpha 2-receptors. Action on other central noradrenergic receptors, and influences on other transmitters must be taken into account when interpreting the effect of clonidine and yohimbine on AGS in rats.
Acoustic Stimulation↗
Psychosocial problems in adults with epilepsy: comparison of findings from four countries.
Psychosocial problems in groups of adults with epilepsy from Canada, Finland, the German Democratic Republic, and the United States were evaluated by the Washington Psychosocial Seizure Inventory. A number of similarities in psychosocial concerns were found across the four countries. At the forefront for each group were emotional problems, followed by concerns pertaining to adjustment to the seizures themselves. Where far-reaching governmental support of a financial and vocational nature was lacking, difficulties in these areas were also noted. In all cases, few problems were found in matters pertaining to family relationships and to medical care. Hypotheses to account for differences between the groups were discussed.
Adolescent↗
A study on benzodiazepine receptor binding in audiogenic seizure-susceptible rats.
Benzodiazepine receptors were investigated in the cerebral cortex, the hippocampus, the brainstem, and the cerebellum of audiogenic seizure (AGS)-susceptible and seizure-resistant (ER) control rats. In AGS-susceptible rats of Sprague-Dawley descent, muscimol (10-6 M and 3 x 10-5 M) activated the binding of 3H-diazepam (0.4 nM) significantly less than in ER-rats. This finding may be strain selective, since it was not observed in AGS-susceptible rats of Wistar descent. Specific binding of the convulsant benzodiazepine receptor ligand methyl 6,7-dimethoxy-4-ethyl carboline-3-carboxylate (3H-DMCM), the benzodiazepine receptor ligand 3H-diazepam and the chloride channel directed cage convulsant t-butylbicyclophosphorothionate 35S-TBPS were not significantly changed in AGS-susceptible as compared to control rats. Our findings indicate that a disturbance at the level of the benzodiazepine receptor/GABA receptor/chloride channel complex is not a likely general aetiological factor for audigenic seizures in rats.
Acoustic Stimulation↗
Tofizopam enhances the action of diazepam against tremor and convulsions.
Tofizopam, an anxiolytic 3,4-benzodiazepine, increases the affinity of benzodiazepine receptors for 1,4-benzodiazepines. In this study we investigated whether this increased affinity of the receptors alters the sensitivity of mice to tremor and to convulsions. Convulsions induced by harmane were not affected by tofizopam (50-300 mg/kg), but diazepam (15 mg/kg) increased the ED50 of harmane from 9.9 to 25.1 mg/kg. Tofizopam did not alter the threshold for electroshock-induced convulsions, while a dose of 10 mg/kg diazepam protected mice from convulsions. Low doses of tofizopam (12.5-25 mg/kg) sensitized mice to the tremorogenic effect of harmaline. Diazepam inhibited tremor: the ED50 of harmaline increased by 153% after 50 mg/kg of diazepam. In contrast to 1,4-benzodiazepines, tofizopam has no anticonvulsive effect. It sensitises mice to the tremor induced by harmaline. In combination with diazepam, however, tofizopam enhanced the anticonvulsive and antitremorogenic actions of this 1,4-benzodiazepine by 12-65%. This effect probably results from a tofizopam-induced increase in the occupation of benzodiazepine receptors.
Animals↗
Strain differences in regional brain histamine levels between genetically epilepsy-prone and resistant rats.
In order to further elucidate the possible role of histamine in the seizure model, we determined the histamine levels in different brain regions of genetically epilepsy-prone Krushinski-Molodkina (KM) rats. Histamine levels in the striatum, hippocampus, amygdala, midbrain, thalamus and hypothalamus of KM rats were significantly lower than in the epilepsy-resistant Wistar rats. Previously, we have reported that the audiogenic seizures of KM rats were reduced by metoprine, which can markedly increase brain histamine. These findings are in agreement with the hypothesis that central histamine neuron system may be involved in the inhibitory mechanism of seizures.
Acoustic Stimulation↗