I.S. Midzyanovskaya

On-off intermittency in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy

In the present paper we consider the on-off intermittency phenomena observed in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy. The method to register and analyze the electroencephalogram with the help of continuous wavelet transform is also suggested.

Dopamine-dependent nature of depression-like behavior in WAG/Rij rats with genetic absence epilepsy

WAG/Rij rats given placebo showed a depression-like state as compared with normal Wistar rats (lacking convulsive pathology); this was analogous to the state previously seen in rats of this line, with decreased investigative activity in the open field test, increased immobility in the forced swimming test, and decreased consumption and preference for sucrose solution (anhedonia). Chronic administration of the tricyclic antidepressant imipramine (15 mg/kg, i.p., 15 days) had therapeutic (antidepressant) effects on depression-like behavior in WAG/Rij rats. After withdrawal of antidepressant therapy, the behavior of WAG/Rij rats was not significantly different from that of Wistar rats. Acute (single-dose) administration of the selective dopamine D2/D3 receptor antagonist raclopride (100 µg/kg, i.p., 15 min before the start of behavioral testing) increased the symptoms of depression-like behavior and suppressed the antidepressant effect of chronic administration of imipramine in WAG/Rij rats. Raclopride had no significant effect on behavior in Wistar rats. Administration of the dopamine D2/D3 receptor agonist parlodel (a therapeutic form of bromocriptine) cured the depression-like behavior of WAG/Rij rats and had no significant effect on behavior in Wistar rats, with the exception of a reduction in the duration of immobility in the forced swimming test. Imipramine and raclopride had no significant effect on the levels of total movement activity and anxiety in either WAG/Rij or Wistar rats. These results demonstrate the dopamine-dependent nature of depression-like behavior in WAG/Rij rats and show the possible involvement of dopamine D2 receptors in mediating the antidepressant effect of imipramine on genetically determined depression-like behavior in WAG/Rij rats.

Time-frequency analysis of spike-wave discharges using a modified wavelet transform.

The continuous Morlet wavelet transform was used for the analysis of the time-frequency pattern of spike-wave discharges (SWD) as can be recorded in a genetic animal model of absence epilepsy (rats of the WAG/Rij strain). We developed a new wavelet transform that allows to obtain the time-frequency dynamics of the dominating rhythm during the discharges. SWD were analyzed pre- and post-administration of certain drugs. SWD recorded predrug demonstrate quite uniform time-frequency dynamics of the dominant rhythm. The beginning of the discharge has a short period with the highest frequency value (up to 15 Hz). Then the frequency decreases to 7-9 Hz and frequency modulation occurs during the discharge in this range with a period of 0.5-0.7 s. Specific changes of SWD time-frequency dynamics were found after the administration of psychoactive drugs, addressing different brain mediator and modulator systems. Short multiple SWDs appeared under low (0.5 mg/kg) doses of haloperidol, they are characterized by a fast frequency decrease to 5-6 Hz at the end of every discharge. The frequency of the dominant frequency of SWD was not stable in long lasting SWD after 1.0 mg/kg or more haloperidol: then two periodicities were found. Long lasting SWD seen after the administration of vigabatrin showed a stable frequency of the discharge. The EEG after Ketamin showed a distinct 5 s quasiperiodicity. No clear changes of time-frequency dynamics of SWD were found after perilamine. It can be concluded that the use of the modified Morlet wavelet transform allows to describe significant parameters of the dynamics in the time-frequency domain of the dominant rhythm of SWD that were not previously detected.

Distribution of D1-like and D2-like dopamine receptors in the brain of genetic epileptic WAG/Rij rats

The densities of the dopamine (DA) D1-like and D2-like receptors were studied by autoradiography in brain regions of rats with (WAG/Rij strain) and without (ACI strain) genetic absence epilepsy. The core of the nucleus accumbens in WAG/Rij rats had a lower density of D1-like receptors than in ACI rats, a reduction of both D1-like and D2-like DA receptors was also found for the dorsal striatum (dorsal caudate-putamen). On the other hand, the density of D2-like receptors was higher in cortical (frontal and parietal) regions and lower in the CA3 region of the hippocampus of WAG/Rij, as compared to ACI rats. These results give new information about possible malfunction of the brain dopaminergic system in the WAG/Rij rat model of absence epilepsy. It seems that there are differences between WAG/Rij and other models of absence epilepsy, especially concerning the role of striatum.

The brain 5HTergic response to an acute sound stress in rats with generalized (absence and audiogenic) epilepsy

The brain serotoninergic (5HTergic) system of epileptic subjects can influence their vulnerability to stress. We studied the putative dependency of 5HT neurotransmission parameters on emotional stress, and the presence, types and severity of seizures using rats with genetic generalized (absence and/or audiogenic) epilepsy, of WAG/Rij and Wistar strains. The animals were stressed by exposure to a short aversive noise or left without sound stimulation. Tissue concentrations of 5HT, tryptophan (TRT) and 5-hydroxyindolacetic acid (5HIAA) were assessed by HPLC. The stressor activated the 5HTergic system within thalamus (5HIAA elevated), frontal cortex (5HT, TRT elevated), hypothalamus (increased TRT) in all rats. However, the normal (non-epileptic) rats displayed the highest response in the frontal cortex and the lowest one in the thalamus, as compared to the epileptic rats. Absence-epileptic rats exhibited higher thalamic 5HIAA increase than their controls. Significant correlations existed between propensity of absence epilepsy and 5HTergic parameters measured in the cortex and hypothalamus of absence-epileptic rats. No major difference was found between groups with and without audiogenic epilepsy. The results imply that the stress response depends on the presence of epileptic pathology and the seizure type and severity. The brain 5HT may be involved in the control of the paroxysms and behaviour in absence-epileptic subjects.

The effects of vigabatrin on spike and wave discharges in WAG/Rij rats.

The effects of vigabatrin, which increases GABA concentrations by inhibiting GABA transaminase, on spike and wave discharges (SWDs) in the electroencephalogram of WAG/Rij rats were studied. Vigabatrin increased the incidence and duration of the SWDs, suggesting a quantitative GABA(A)ergic involvement in the mechanism(s) underlying the starting and stopping of an ongoing SWD. Also, vigabatrin decreased the SWD peak frequency, suggesting an important role of GABA(B) in the mechanism(s) underlying the peak frequency of the SWDs. Vigabatrin gradually changed the course of the hazard rates of the SWD durations, suggesting a qualitative GABAergic role in the mechanism(s) underlying the stopping of an ongoing SWD.

Brain histamine in the WAG/Rij rat, an animal model of absence epilepsy

The involvement of brain histamine in epileptogenesis has been studied in convulsive epilepsies [1], but not non-convulsive ones. As histamine controls the arousal maintenance, it possibly has a role in “paroxysmal loss of consciousness” (absence epilepsy) [2]. We have used the WAG/Rij rat strain as a model for absence epilepsy. This brain pathology manifests as spike-wave discharges (SWDs) in EEGs. Up to 95% of WAG/Rij rats display SWDs, mostly during passive awake or slow-wave sleep states. Minor behavioral changes, and unresponsiveness to external stimuli accompany SWDs [3, 4]. Additionally, about 30% of WAG/Rij rats show audiogenic convulsions, thus being a model for mixed epilepsy (absence epilepsy and audiogenic epilepsy).

Metoprine induced behavioral modifications and brain regional histamine increase in WAG/Rij and Wistar rats

The effects of metoprine, an inhibitor of histamine N-methyltransferase, on open field activity and brain regional histamine (HA) content were examined in rats with mixed, absence and audiogenic, epilepsy (WAG/Rij-AGS), rats with audiogenic epilepsy (Wistar-AGS) and in non-epileptic control rats (Wistar-nAGS). HA content was increased by metoprine (20mg/kg, i.p.) in the cortex, striatum, thalamus, hypothalamus and hippocampus of the rats from all three tested groups. However, WAG/Rij rats showed a lower rate of metoprine-induced HA accumulation in the striatum and thalamus than Wistar rats. For the open field test, the main effect of metoprine (20mg/kg, i.p.) was a general increase of locomotor activity although distinctive features, such as hyperlocomotion and exaggerated sniffing, were characteristic for the epileptic rats (WAG/Rij-AGS and Wistar-AGS, respectively). Individual rats from all the groups showed stereotyped behavior of shuttle type and head bobbing. Electroencephalographic data obtained in WAG/Rij-AGS rats confirmed that metoprine-induced behavioral activation was accompanied by suppression of spike-wave discharges, the main hallmark of absence seizures. Taken together, these results show that inhibition of the histamine catabolism may induce motor activation of particular patterns in epileptic rats and provoke stereotyped behavior.

Regularities of Alternate Behavior in Spontaneous Nonconvulsive Seizure Activity in Rats

275 The study of the complicated behavior of ensembles of neuronal elements is of great interest. In this connection, the brain, which is a very complicated neuronal ensemble, is an interesting object for investigation. The brain research is of theoretical interest and has a great importance because the study of fundamental laws of brain function helps to find the reasons of origin and development of pathologies in the central nervous system [1]. Processes in the brain are often studied using approaches based on the construction of relatively simple models of single neurons [2], which are subsequently connected together [3]. The next stage in the development of the models in question is the consideration of chains, lattices, and networks consisting of elements that model single brain structures [4]. Evidently, the results obtained using such models should be compared with the results obtained in the experiments. Another approach is the study of experimental time series and their analysis by methods of nonlinear dynamics [5, 6]. In particular, it is worth mentioning the report [7] in which the authors attempted to determine the direction of the links between different regions of the brain cortex to diagnose their functional interaction.

Dual effect of pyrilamine on absence seizures in WAG/Rij rats

No Abstract..