FREE-RADICAL OXIDAION OF PROTEINS IN BRAIN OF RATS WITH EXPERIMENTAL BLOCKING OF GABA RECEPTORS

Abstract

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The disturbance of GABA and corticoliberinenergic system of hypothalamus systems interaction is the basis for many post-stress disorders. And an original strategy of adaptive behavior is one of the reasons for the development of different types of psychopathology. We have established that animals with differences in individual and typological characteristics of neurotic system differ by the whole range of biochemical parameters, including sign indices like oxidative modification of proteins (OMP). Previously we showed that the group of active Wistar rats, selected with the use of T-maze, connects high- and low-anxiety animals with different individual sensitivity towards the action of corticoliberin; in low-anxiety rats (LA) corticoliberin increases the level of anxiety, while high-anxiety rats (HA) are resistant to it. Purpose of the work: was to study the dynamics of OMP in hypothalamus and cerebral cortex of active Wistar rats of, which differed by the anxiety level and sensitivity to corticoliberin, in response on blocking of GABA receptors as the result of microinjection of picroroxine in the third cerebral ventricle. Material and methods of the work: Wistar active rats were selected in a T-maze. Then while tests in the elevated plus maze (EPM) low- and high-anxiety animals were selected. Every animal was implanted with lines with steel cannulas under narcosis (rometar-zoletil) on stereotaxic coordinates (more caudal than bregma by 1.0 mm, more lateral than the midline of a skull by 1.0 mm) to inject the solutions into third cerebral ventricle. Control animals were injected with NaCl 0.9% (5 µl), experimental animals were injected with picrotoxin at dose 5ng in 5 µl, and then after 30 minutes the effect of the substances injected was studied in the EPM. After the tests rats were decapitated, and in the cortex of big semi-spheres and hypothalamus we determined the level of OMP by using Levine et al. method (1990). We used the indices of spontaneous OMP (SOMP - basal level of protein oxidation) and OMP induced by Fenton’s reagent (FOMP index of system resistance to the peroxidation). Results of the study: GABA receptors blocking with picrotoxin lowers the reactive anxiety level in LA and HA in comparison with the control (increases the duration of presence in open arms of the EPM, increases the number of overhangings from the open arms). HT group shows the highest excitement, eliminating the anxiety entirely. In control groups OMP in the cortex of LA rats is lower than in HA rats. After the injection of picrotoxin OMP in cortex of LA group is almost unchangeable, while spontaneous (SOMP) and induced (FOMB) groups, OMP constituents, decrease. In hypothalamus of control groups of SOMP in LA rats is higher and FOMP is lower than in HA rats. After the introduction of picrotoxin the correlation of OMP in the studied groups changes to the opposite; LA rats have SOMP decreased, and HA rats have SOMP increased up to the control indices of LA rats. Conclusions: thus, the decrease of anxiety level in LA rats with GABA receptors blocking is connected with the inhibition of OMP processes in hypothalamus of these animals. While the decrease of anxiety level in HA rats in the response of picrotoxin effect is connected with the decrease of OMP level in the cortex and increase of OMP level in hypothalamus. Thus, we suppose that moderate blocking of GABA receptors has an adaptive effect on LA animals.