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A study is performed of the effect of the convulsants picrotoxin and bicucuUine, blockers of GABA-dependent C1--conductivity, on the rate of desensitization of muscimol-induced ~6C1-entry into synaptoneurosomes isolated from rat cortex. Both picrotoxin and bicuculline, despite the difference in the mechanisms of inhibition of the GABA receptor/C1-ionophore complex, markedly reduce the rate of desensitization. However, the initial moment of the action of both convulsants is characterized by inhibition of C1-transport alone, without a drop of the rate of desensitization.Key Words: desensitization; picrotoxin; bicuculline; synaptoneurosomes The GABA receptor/C1-ionophore complex is one of the most important molecular structures of preand postsynaptic membranes. Binding of GABA or its agonists (in particular, muscimol) with the GABA receptor opens up the coupled C1-channel and leads to a transient increase of the C1-permeability of neuronal membranes and, correspondingly, to spike inhibition. Long-term action of the transmitter results in desensitization of the receptor/ionophore complex, i.e., in a decrease of GABA-dependent C1-permeability [2,3].In our previous study we showed that pentylenetetrazole inhibition of muscimol-dependent 36C1 entry into synaptoneurosomes is accompanied by a considerable delay of desensitization. Here we report on experiments with the classic blockers of the GABA receptor/C1-ionophore complex bicuculline and picrotoxin, which act through different mechanisms. Bicuculline inhibits binding of GABA with the GABA receptor in a competitive manner MATERIALS AND METHODSIn our experiments we used the methods described earlier [1] with some modifications.White random-bred male rats weighing 180-200 g were decapitated, and the cerebral cortex was removed and homogenized manually (5 frictions) at 0-4~ in a glass homogenizer with a Teflon pestle in Krebs-Ringer medium containing (in mM): 145 NaC1, 5 KC1, 1 MgSO 4, 1 CaC 89 10 glucose, and 10 HEPES, pH 7.4 (20~ 15 ml/g tissue). The homogenate was sequentially •tered through 300-, 99-, 60-, and 27-~t capron sieves (Rakhmanov plant, Russia). The filtrate was centrifuged at 2700 g for 5 min, resuspended in the same volume of KrebsRinger medium, and recentrifuged under the same conditions. After the second centrifugation the pellet was suspended in Krebs-Ringer solution so that the final concentration of synaptoneurosomes was 4

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Electrophysiological experiments on Wistar rats demonstrated that prior immunization of animals with conjugates of dopamine and serotonin with bovine serum albumin, as well as with bovine serum albumin alone, played a partial protective role in relation to the subsequent development in these animals of experimental MPTP-induced depressive syndrome: immunized animals showed no signs of the depressive state such as decreases in the latency of onset of REM sleep and the development of epileptiform activity in the caudate-putamen complex, though the increase in the proportion of REM sleep in the overall structure of sleep persisted. Changes in the spectral characteristics of brain electrical activity and sleep structure during the development of experimental MPTP-induced syndrome in animals immunized with conjugates of dopamine and serotonin with bovine serum albumin and with bovine serum albumin alone were antigen-specific and reflected functional shifts in the activity of those neurotransmitter systems targeted by immunization, as well as others sensitive to changes in the body's immunological status.

Damage to the nervous system is a causal and conditioning event leading to the development of pathological processes mediated via such endogenous mechanisms as the tormation of integrative complexes from damaged and secondary changed nervous structures that are pathological by their nature, mechanisms, and effects. At the level of neural relationships such pathological integrative complex (PIC) is formed by an aggregate of hyperactive neurons (generator of pathologically enhanced excitation, GPEE) producing uncontrollable ongoing flow of nerve impulses. At the systemic level, PIC is a new pathodynamic system composed of various subdivisions of the CNS, which acts as a pathological system. The subdivision of the CNS containing GPEE assumes the role of a pathological determinant due to its enhanced activity. This pathological determinant induces the tormation of a pathological system and controls its activity at the early period of its genesis. Every neuropathological syndrome is a clinical or behavioral manifestation of pathological system activity. Pathological determinant and pathological system are general biological categories that fall outside the scope of nervous disorders. They can arise in various systems at the micro-and macroscopic levels and induce systemic pathology.