Inhibition of metaphit-induced audiogenic seizures by APV in rats.

The influence of APV ((+/-)-2-amino-5-phosphonovaleric acid) on EEG activity and behavior was studied on a model of epilepsy induced by intraperitoneal administration of metaphit (1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine). Male Wistar rats received an injection of metaphit (10 mg/kg) and were subjected to intense audio stimulation (100+/-3 dB, 60 s) at hourly intervals during the experiment. The seizures were classified according to a four point scale ranging from 0 (no seizure) to 3 (tonic convulsions). In our report we studied the time course which revealed the maximum incidence and severity of seizures 7-12 h after the injection (10 out of 12 rats, with severity of 2.25+/-0.32). APV (0.05, 0.1, 0.2 and 0.3 micromol) was injected intracerebroventricularly at the time of fully developed convulsions. APV inhibited seizures in a dose-dependent manner. The minimum dose, which completely blocked seizures in all animals, was 0.3 micromol, while ED50 were 0.11, 0.10 and 0.07 micromol against running, clonus and tonus, respectively. In contrast to behavioral inhibition of convulsions, metaphit-provoked epileptiform activity was not abolished by APV, and represented a prerequisite for the reappearance of behavioral seizures. It is suggested that APV is rather an anticonvulsant than an antiepileptic agent in this model of epilepsy.     

Biological responses of audiogenic stress

Biological effects of prolonged exposure to sound waves (17 kHz) on developing female rats were examined. Rat pups of day 80 were grouped into two. Experimental group was exposed to sound waves and control group, who were not so exposed. Daily food, water intake were measured in developing animals and spontaneous motor activity, electrocardiogram and blood sugar were studied in adults. It was found that the experimental group of animals behaved differently from the control group. It is concluded that the sound waves produced changes in the animals which were within the physiological limits but were suggestive of development of stress.     

A novel gene causing a mendelian audiogenic mouse epilepsy.

Frings mice are a model of generalized epilepsy and have seizures in response to loud noises. This phenotype is due to the autosomal recessive inheritance of a single gene on mouse chromosome 13. Here we report the fine genetic and physical mapping of the locus. Sequencing of the region led to identification of a novel gene; mutant mice are homozygous for a single base pair deletion that leads to premature termination of the encoded protein. Interestingly, the mRNA levels of this gene in various tissues are so low that the cDNA has eluded detection by standard library screening approaches. Study of the MASS1 protein will lead to new insights into regulation of neuronal excitability and a new pathway through which dysfunction can lead to epilepsy.     

听源性惊厥致P77PMC大鼠杏仁核内胆囊收缩素mRNA短暂性增加

铃声刺激诱发惊厥 ,原位杂交法检测遗传性听源性癫痫易感大鼠 (P77PMC)一次与多次惊厥发作对杏仁核内胆囊收缩素 (CCK)mRNA含量的影响。结果发现 :( 1)惊厥未发作组大鼠杏仁核单位面积内的CCKmRNA阳性神经元数 (No/ 0 0 1mm2 )较少 ,为 8± 1;( 2 )惊厥发作一次组大鼠杏仁核单位面积内CCKmRNA阳性神经元数显著增加 ,发作后 30min时达到峰值 ,为 5 8± 5 (P <0 0 1) ,但是 2h后迅速降为正常 ,为 9± 2 (P >0 0 5 ) ;( 3)惊厥多次发作组大鼠在惊厥发作后 30min时 ,CCKmRNA阳性神经元数亦显著增加 ,为 2 2± 3 (P <0 0 1) ,但明显低于惊厥发作一次组大鼠 (P <0 0 1) ,1h即恢复正常 ,为 9± 3 (P >0 0 5 )。结果表明 ,惊厥发作后P77PMC大鼠杏仁核内CCKmR NA含量呈现迅速而短暂增加的特点 ,表明CCKmRNA参与惊厥的急性发作过程 ,提示CCKmRNA在惊厥发作早期阶段发挥了重要的抗惊厥作用     

Psychoactive compounds and audiogenic seizure susceptibility

The purpose of these experiments was to gain comparative information about psychoactive compounds on experimental convulsions, a phenomenon that has been used as an index of CNS excitability. LSD, mescaline, d- and 1-amphetamine, cocaine and morphine were all effective in blocking audiogenic seizure susceptibility. None of the compounds were effective in blocking the priming of a non-susceptible strain of mice. This latter finding differentiates these compounds from Δ⁹-tetrahydrocannabinol which has been previously reported to block priming.     

Linear relationship between stimulus intensity and audiogenic seizures in inbred mice.

An examination of the manifestations of convulsive seizure activity in hundreds of inbred audiosensitive O'Grady mice exposed to auditory signals revealed that, apart from the maximal manifestation itself, the lag time prior to its obset is a suitable criterion for evaluation of the seizure response. Following exposure of a random population of 100 inbred mice to a fixed signal of average intensity which led to approximately 60% of tonic seizures, a scale of weighted values was designed. Animals responding with the maximal tonic seizures were subdivided further according to the lag time to the onset of response. Each group was assigned a value number. A scale of responses of individual mice, ranging from 1 to 10 points, approximately equivalent in terms of distribution of responses, was constructed thereby; individual results could be summed up for group totals. The statistical validity of the scale was proved in 583 typical inbred mice picked at random. Its usefulness was established when the evoked response of a group increased with increased stimulus intensity, the relationship being nearly linear between 69 and 85 dB, at 22 KHz. Group responses to signals of fixed sound pressure at frequencies ranging from 8 to 17 KHz were found to follow a bell-shaped response curve with peak seizure activity near 13 KHz, the frequency corresponding to the greatest mouse hearing acuity.     

Activity of cholinergic system enzymes in the cochlea of mice sensitized for audiogenic seizure.

Activity of the enzymes of cholinergic system was investigated in the cochlea of mice sensitized for audiogenic seizure by priming and compared with genetically audiogenic seizure susceptible mice. Higher choline acetyltransferase activity was found in the cochlea of primed mice as well as in the cochlea of audiogenic seizure susceptible mice as previously stated. A possible interpretation of these data is discussed.     

Mechanisms underlying modifications in the severity of audiogenic convulsions

Catecholamine levels were selectively decreased in peripheral sites or in brain of mice by intravenous or intraventricular injections of 6-hydroxydopamine. Brain dopamine alone was decreased by administering i.p. desmethylimipramine prior to 6 hydroxydopamine injections. A brain noradrenaline decrease does not induce mortality in a tonic strain of mice but can transform clonic audiogenic seizures into tonic seizures in a clonic mouse strain, while a dopamine depletion alone has no effect. However, a noradrenaline decrease at peripheral sites increases the number of lethal seizures in a tonic strain without modifying clonic seizures in a clonic strain. Catecholamine metabolism is neither involved in the onset of seizures in a non-sensitive strain nor involved in the change of clonus into tonus in unilaterally deafened tonic strain animals, which in this case present only clonic seizures.     

The effect of acetyldexphenmetrazine and dexphenmetrazine on the susceptibility to audiogenic seizures in mice.

The antiepileptic effect of dexphenmetrazine (DP) and acetyldexphenmetrazine (ADP) was tested on audiogenic seizures in a 100% susceptible strain of mice. DP had no antiepileptic effect, however, it markedly suppressed the postparoxysmal motor inhibition. ADP had a distinct anticonvulsive effect--it suppressed the convulsive component of the seizure, leaving its running component unaffected. The results are compared with the effect of both drugs on electrographic epileptic phenomena in the turtle brain (Servít and Strejcková 1976).     

Listen carefully: positional cloning of an audiogenic seizure mutation may yield Frings benefits.

Neurologists have long sought to understand what precipitates individual seizures in epileptic patients. Studies of reflex epilepsies seem well suited to this task. In this issue of Neuron, Skradski et al. describe a mutation in a novel gene underlying audiogenic seizures in the Frings mouse, providing a valuable resource for elucidating the pathophysiological mechanisms of this inherited form of reflex epilepsy.     

Characteristics of lateralization in rats prone to audiogenic epilepsy

Differences in asymmetry of audiogenic seizure susceptible rats (ASS) as compared with resistant rats (ASR) were analysed in the present study. It was found that ASS rats were more lateralized in behavioral tests (the choice of one side of T-maze and the preference of one paw in obtaining food from the tube) and after systemically injected apomorphin. It was also established that there were more sexual differences of asymmetry in the ASS group than in the ASR one.     

Effect of neonatal 6-hydroxydopamine treatment on audiogenic seizures

Subcutaneous injection of 6-hydroxydopamine (6-OHDA) in newborn audiogenic rats resulted in an increase in convulsive seizure intensity and a decrease in norepinephrine concentration in the cerebral cortex and the spinal cord. In addition, norepinephrine concentration in the brainstem (pons-medulla) was increased. Dopamine concentration in all brain regions studied was unchanged. The results suggest that norepinephrine exerts its modulatory influence on convulsive seizures by an action in either the spinal cord, the cerebral cortex, or both.