NEW TRANSLATIONAL MODEL OF COGNITIVE DEFICIT IN SCHIZOPHRENIA

DOI: https://doi.org/None

Bondarenko N.A., Ostrovskaya R.U., Gudasheva T.A., Durnev A.D.

Introduction. Taken into account the literature data on the leading role of perceptual deficit in the pathogenesis of schizophrenia and the lack of experimental models of this impairment we proposed the novel test of instinctive aversion (TIA). The work was performed in order to evaluate the translational validity of this test in the study of the effect of different neuroleptics: representing the group of typical, atypical neuroleptics, as well as novel,neurotensin dipeptide analogDilept in TIA test and to compare with their activity in tests commonly used for screening of neuroleptics : apomorphine (APO) induced climbing and l-DOPA induced disturbance in the test of extrapolative escape (TEE). Methods. Experiments were performed on outbred rats (TIA and TEE) and CC57/W mice (climbing test) by using the equipment of «Open Science» Company. APO in doses of 2 mg/kg and l-DOPA (Madopar) in doses of 125 mg/kg were administered subcutaneously or intraperitoneally correspondingly. Results. All neuroleptics under study independently on their chemical structure demonstrated the ability to ameliorate the effect of APO in TIA. Their activity was confirmed in standard tests. TIA was shown to exist in adult (PD 90) or youngsters (PD 50) only, but not in immature rats. Peculiarities of neurochemical mechanisms underlying the effect of APO and L-DOPA are proposed to be a reason of certain difference in the level of threshold doses for all three tests. Conclusion. The suggested model meets criteria of constructive, obvious and predictive validity and is suitable for the screening of neuroleptics.
Keywords: 
schizophrenia, modeling of cognitive deficits, antipsychotics, Dilept, neurotensin dipeptide analogue
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