Results

Discussion

REFERENCES

We report here a comparative analysis of the acquisition of a conditioned passive avoidance reaction in mice of the mutant strains DISC1-Q31L and DISC1-L100P and mice of the control strain C57Bl/6NCr1 and detection of the effects of gender and age on learning. DISC1-L100P mice showed impairments to associative learning to avoid the dangerous dark sector of the apparatus regardless of gender and age. In DISC1-Q31L mice, the fear memory trace formed only in young males. A defi cit of aversive learning was demonstrated in old mice of all the strains tested, with identically lower levels of learning ability in female DISC1-Q31L and C57Bl/6NCr1 mice than males. These characteristics of learning avoidance provide an additional argument for regarding DISC1-L100P mice as a genetic model of a schizophrenia-like state and DISC1-Q31L mice as a model of a depression-like state.The ability to identify threats in the surrounding world and mount targeted responses to them are critical for adaptation of the body. Fear is a fundamental adaptive manifestation of behavior supporting survival [15]. This adaptive function is linked with the potential for rapid and consistent acquisition of associations between neutral stimuli, including context, and a negative event. A typical example of such associative learning is the conditioned fear reaction. Paradigms forming fear memories (classical conditioned fear reaction, fear-potentiated twitch reactions, conditioned passive avoidance reactions) are very widely used for identifying the neuronal and molecular mechanisms of memory in studying cognitive impairments in psychopathological states using experimental models. As the genetic component determines the risk of developing psychopathology [17], many investigators display considerable interest in studying fear memory in mice of inbred and genetically modifi ed strains [1, 2, 21, 29, 35, 39]. The genetic factor has been shown to have a signifi cant infl uence on the neuronal processes of fear memories, including learning, consolidation, retention, and extinction of the memory trace. Finding an experimental model in rodents with the full set of pathological signs of any disease is very diffi cult. In the cases of schizophrenia and depression, this is made more complex by the heterogenous nature of the symptoms and diffi culties in establishing a reliable pathological etiology [34]. Among a multitude of experimental models of these diseases, the greatest interest in recent years has been in genetic models with impairment of the DISC1 gene (Disrupted in Schizophrenia 1), which has a very strong link with the development of schizophrenia and depression [16, 27, 31, 36]. Two mouse strains were created carrying point mutations in exon 2 of the DISC1 gene – DISC1-L100P (substitution of a leucine by proline at position 100), which is regarded as a genetic model of a schizophrenia-like state, and DISC1-Q31L (replacement of glutamine by leucine at position 31), which is regarded as a genetic model of a depression-like state [8, 27]. The behavioral profi les of DISC1-L100P and DISC1-Q31L mice were shown by these investigators to differ from the behavioral profi le of mice of the control strain C57Bl/6NCr1 [8, 25, 26].