Российская академия наук


Dynamic processes associated with increased of



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Dynamic processes associated with increased of spikE-wave discharges in WAG/RIJ rats strein

Fedosova E.A., Sarkisova K.Yu, Bazyan A.S.

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia;


WAG/Rij rats strain are genetic model of man absence epilepsy. Absence epilepsy develops in WAG/Rij rats gradually. The first spike–wave discharges appear in rats of 2 – 3 months age. A full spike–wave discharges deployed to 5-6 months. The absence spike–wave discharge generated by Ih pacemaker channel, is the hyperpolarization activated pacemaker channel, which works in tandem with low-threshold T-type Ca2+ channel. Patch–clamb registration, Western blot analysis showed that the age-dependent increase of spike–wave activity, accompanied by a decrease in the number of HCN1subunits protein [Kole et al., 2007]. It turns paradoxical at first glance, the situation. Changes in the activity of Ih channel is accompanied by a change of the spike–wave discharges, but in inverse proportion. At least that is the supposed author of the work described. We describe these experimental results using a quantitative model and showed that this orientation process is associated with the properties of HCN1 and HCN2 subunits.

But along with increasing spike–wave activity in WAG/Rij rats growing the deficit of meso-cortico-limbic DA system, which is 5-6 months to reach a level that causes these rats pronounced depressive behavior. The purpose of the experimental part of the study was to investigate the concentration of monoamines and their metabolites in 2 month old rats, a study of their behavior on equipment possible to describe depression (forced swimming) and anxiety (light and dark choice) and general motor activity in the open field. In the prefrontal cortex revealed significant differences between Wistar and WAG/Rij rats strains. In all other structures: the nucleus accumbens, hypothalamus, striatum, hippocampus, no significant differences between Wistar and WAG/Rij rats is not revealed. The introduction of L-DOPA the precursor synthesis of DA, in a low dose of 25 mg/kg, showed a uniform increase in the concentration of DA in all the structures of the brain in both strains of rats. The results indicate an increased sensitivity prefontalnoy cortex, which we explain the involvement of this structure in cognitive functions, including making decision. Structures associated with emotional states and the states of depression and anxiety: the nucleus accumbens, hippocampus, hypothalamus, and do not reveal differences. Similarly, no significant differences found in the forced swimming test and the light-dark choice. Significant differences were not detected in the striatum, a structure responsible for motor control. According to this there were no differences in locomotor activity, which were investigated in the open field test.



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