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The role of GABAergic mechanisms in realization of the effects of afobazole and picamilon on the cerebral circulation was studied in rats. It is found that the cerebrovascular effect of afobazole significantly decreases on the background of the GABA receptor antagonists bicuculline and picrotoxin. This is evidence of an important role of the GABA system in the its cerebrovascular and neuroprotective activity of afobazole. The results of experiments with picamilon showed that the cerebrovascular effect of this drug is not affected by receptor blocking with bicucullin. However, the blocking of chloride channels of the GABA receptors by picrotoxin significantly decreased the effect of picamilon on the cerebral blood flow.

A seizure-protecting effect of the delta-sleep-inducing peptide (DSIP) and its analogues was revealed. An intensive sorption of H3 tryptophan occurred under the effect of the DSIP and its analogues. The data obtained suggests that the serotoninergic system plays no important part in the seizure-protecting effect.

Picrotoxin administration decreased the incorporation of labelled phosphate in neurospecific protein synapsin I in vitro in cortex. In the animal hippocampus, the incorporation was more expressed. The data obtained suggest that activation of the cAMP-dependent phosphorylation occurs during seizure in the cortex.

The effects of delta-sleep inducing peptide (DSIP) and its analogues (1-4) administered into substantia nigra pars reticulata on locomotor and seizure activity were estimated in experiments in rats. It was shown that intranigral microinjection of DSIP as well as DSIP-1-DSIP-4 caused decreasing of horizontal, vertical locomotor activity and attendance of central sectors of the "open field". Antiseizure effects, i.e. the first and clonic-tonic picrotoxin-induced convulsive latent period lengthening and their intensity decreasing, revealed DSIP, DSIP-2 and DSIP-3. Authors suppose that changes of DSIP structure lead to changes of effects expression on locomotor and seizure activity in conditions of their administration into substantia nigra reticulata. Obtained data concerning protective effects of studied peptides on experimental seizure syndrome allow to conclude that there is interaction between DSIP-induced hypokinesia and DSIP analogues anticonvulsive effectiveness in case of their intranigral administration which is likelihood is one of the component of nigral-dependent seizure-suppressive mechanism.

Activated lipid peroxidation observed in brain homogenates in experimental choreoid hyperkinesis and bemegride epilepsy can be arrested by antioxidant pretreatment. The same is true for parkinsonian and "malignant locomotion" syndromes provoked by intrastriatal pro-oxidant (oxidized oleinic acid) microinjection and systemic administration of haloperidol. Experimental therapy of choreoid hyperkinesis with GABA-positive and dopamine-blocking drugs alone proved ineffective. The effect was achieved at combined application of antioxidant and GABA-positive drugs.

It is shown that both intracerebral and intraperitoneal neurotropin administration resulted in a decrease of seizure susceptibility of preliminary picrotoxin--kindled rats. On the other hand, neurotropin did not change the course of kindling development. Under conditions of acute picrotoxin--induced seizures it was observed that preliminary cycloheximide (protein-synthesis blocker) administration abolished anticonvulsant properties of neurotropin. It is concluded that anticonvulsant effects of neurotropin are realized via modulation of endogenous peptides synthesis and, in particular, cerulein.

The binding of 3H-muscimol and 3H-diazepam to rat striatum membranes after picrotoxin- and bicuculline-induced seizures was characterized. No alteration in the maximal binding capacity (Bmax) of 3H-muscimol was observed. However, bicuculline produced a 27% decrease in Kd. Both picrotoxin and bicuculline increased the binding capacity of 3H-diazepam. Bicuculline produced a 86% increase in Kd. These results suggest that the GABA antagonists-induced seizures may modulate 3H-muscimol and 3H-diazepam binding in rat striatum.

In acute experiments on rats it was shown that activation of SC by bilateral microinjection of penicillin (5-15 IU) or bicuculline (25-50 ng) resulted in the increased latency and decreased severity of i.p. picrotoxin-induced seizures (2 mg/kg). The suppression of behavioral convulsions and the decreased epileptic activity in the hippocampus and cerebral cortex were followed by occurrence of spike discharges in SC with an amplitude of 200-500 mcV and frequency of 5-12/sec which testifies to the formation of penicillin- or bicuculline-induced generator excitation in SC. The lesions of SC by kainic acid administration resulted in the decreased seizure threshold and, also, facilitated the development of seizure under conditions of picrotoxin kindling. The conclusion is made that SC activation plays an important role in the realization of functional integrative activity of the antiepileptic system.

The antiepileptic action of neurotropin (Nippon Zoki Pharmaceutied Co. Ltd., Japan) was investigated in acute experiments on rats, mice and cats. The increasing of latent period of the first seizures which were picrotoxin-induced and enhancing of this type of seizures were observed correspondently in 1-24 hours and 8-9 days after intraventricular neurotropin injection. Intraperitoneal neurotropin injection (0.2-0.5 ml) to mice caused dosage-dependent antiseizure action on the model of generalized picrotoxin-induced seizures. +Anticonvulsant++ effect of neurotropin was observed during five days. The intraventricular neurotropin injection to cats led to strychnine (0.1%) induced cortical foci suppression.

Experiments on isolated mice (CC57W males) have demonstrated that GABA antagonists (bicuculline, picrotoxin, thiosemicarbazide) increase the desocializing effects of isolation (enhance aggression and reduce intraspecies sociability), while GABA-positive drugs (muscimol, gamma-acetylenic GABA) within a certain dosage range diminish aggression and favour a temporary recovery of sociability. It is suggested that GABA deficiency in the CNS of isolated mice is a pathogenetic link responsible for the pathological behavior -- superaggression and hyper-reactivity.