ИСТИНА

The selection of Krushinsky-Molodkina (KM) rat strain had been started in Moscow State University at the end of 1940-s in the Laboratory of Physiology and Genetics of Behavior (Biology Department, Lomonossov Moscow State University) during 75 years and starting from 1989 – as the inbred strain). It is the oldest strain among several audiogenic seizure prone strains. The trait – audiogenic seizure proneness in KM strain - is characterized by high expressivity and penetrance – the short latency (1-2 s) seizure fit with maximal intensity of clonic and then tonic seizures of trunk and extremities musculature. The long lasting postictal catalepsy follows the AE fit. The postictal “audiogenic” catalepsy is also regarded as the perspective laboratory model of another type of brain pathology. Thus, the KM rat strain served as the valuable laboratory model for testing the big range of anticonvulsant drugs (both - already used in clinic and the new ones). Valproate sodium, difeninum, carbamazepin, lamotrigine, levetiracetam and several other anticonvulsants proved to decrease both the intensity and increase the latency of seizure fit in response to sound. The effects of several compounds with different mechanisms of action were also investigated – antioxidants of different chemical groups, pineal hormone melatonin being among them and their anticonvulsant effects were demonstrated. In order to create the more reliable group of control animals which would share the larger part of genotype of AE susceptible KM rats the new selection experiment was initiated in 2001. The aim of this selection was to breed the strain of rats which are related to KM by at least part of genotype but which would be non-prone to AE. The new strain was labeled as “0” strain. The strain which was opposite by the trait expressivity was labeled as ‘4’ (the maximal fit intensity in arbitrary units). The selection of these new strains was started on the basis of F2 hybrid population between KM and Wistar rats (in the latter the individuals which did not manifest AE fit were taken as parents for this cross). In two families which were maintained during selection two backcross generations to KM parents were performed before the selection experiment started. At the end of 2016 there is the 33-th generation of selected “0” and “4” strains, the expression of AE proneness being opposite from one another. The slow increase (44,5% at 33-th generation) in the number of non-prone animals in the “0” strain was also found.and the differences between KM and “0” strains were also found in the intensity of postictal catalepsy. Numerous well established data on AE the high level of reliability and stable AE fit pattern as well as the clinical need for reliable model system to test new anticonvulsants – all this point to AE use for both theoretical (epileptogenesis mechanisms) and practical (preclinical investigations) goals.