Long-term reduction of benzodiazepine receptor density in the rat cerebellum by acute seizures and kindling and its recovery 6 months later by a pentylenetetrazole challenge.

Seizures induced by an acute pentylenetetrazole (50 mg/kg) injection were accompanied by a long-term (at 1-48 h, but not on day 7) decrease in the density (B(max)) of [3H]-diazepam binding to benzodiazepine receptors in rat cerebellar cortex with no change in affinity (K(d)). Kindling for 24 days by daily administrations of pentylenetetrazole (20 mg/kg) led to the same decrease in benzodiazepine receptor density (at 1-48 h, but not on day 7) as that observed after a single dose of pentylenetetrazole (50 mg/kg). This suggests a common mechanism for both acute and kindling-induced seizures, dependent on the long-term receptor changes. The increased susceptibility to seizures persisted for 6 months after the termination of kindling, with BDZ receptor density in cerebellar cortex reduced almost by half. In age-matched controls, an acute dose of PTZ (30 mg/kg) induced seizures and decrease in both B(max) and K(d) of [3H]-diazepam binding. In kindled rats, at 6 months post-kindling, the same dose of PTZ (30 mg/kg) restored the benzodiazepine receptor density to the level found 6 months before, at the time of termination of kindling. Also, the severity of seizures was enhanced in the kindled rats. The results are discussed in terms of a balance of inhibitory and excitatory processes, in which the reduced BDZ receptor density at 6 months post-kindling may represent a compensatory reaction to outbalance some alterations in excitatory systems that have been reported to be induced by kindling.

[The characteristics of higher nervous activity and of the brain benzodiazepine system in rats subjected to ethanol exposure in the prenatal period]. / Osobennosti vysshei nervnoi deital'nosti i benzodiazepinovoi sistemy mozga krys, podvergshikhsia vozdeistviiu étanola v prenatal'nom periode.

Exposure to ethanol during pregnancy results in the alternation of 3H-diazepam binding to synaptosomal neocortical membranes from the rat offspring. In male experimental rats, 14 days of age, binding level diminished to 11%. In two-month-old control rats Scatchard plot was biphasic. It has been shown that prenatal exposure to ethanol leads to changes in the nature of binding in two-month-age experimental animals, as compared with the control ones. 3H-diazepam binding changes went along with behavioural deviations. In experimental rats locomotor activity was increased in the "open field" test, passive avoidance conditioned reflex retention was decreased and elaboration parameters of active avoidance conditioned reflex were changed, as compared with the control ones. The data obtained show that higher integrative functions were disturbed by prenatal alcoholization. Correlations between benzodiazepine receptor state and behaviour were studied.

[The effect of DMCM and diazepam on the behavior of rats subjected to ethanol exposure in the prenatal period]. / Vliianie DMSM i diazepama na povedenie krys, podvergshikhsia vozdeistviiu étanola v prenatal'nom periode.

White rats were given 4 g/lag daily of 40% ethyl alcohol from the 5th till the 20th day of pregnancy. Males of the off-spring from the 5th till 19th day were subjected to treatment with 0.6 mg/kg DMCM (4-ethyl-6, 7-dimethoxy-beta-carboline-3-carboxylate methyl ether) or 2.5 mg/kg of diazepam daily. It has been shown that both drugs normalize increased locomotor activity; treatment with DMCM corrects passive avoidance conditioned reflex retention; both drugs restore active avoidance conditioned reflex elaboration in rats alcoholized prenatally. Moreover, treatment with DMCM or diazepam restores correlations between behaviour indices and binding of 3H-diazepam which have been altered by prenatal alcoholization.

[The properties of the benzodiazepine receptors of the rat cerebellum 6 months after korazol-induced kindling and recurrent seizures]. / Svoistva benzodiazepinovykh retseptorov mozzhechka krys cherez shest' mesiatsev posle korazolovogo kindlinga i povtornykh sudorog.

It was shown that the increased brain seizure readiness persisted within 6 months after termination of corazol kindling. Seizures of the same severity as during kindling (corazol injection in a dose of 20 mg/kg) were reproduced by corazol injection in a dose of 30 mg/kg. In contrast to the control rats, in this situation an autoenhancement of seizures was observed in the kindled animals. Acute corazol seizures induced a decrease in Bmax and Kd of 3H-diazepam binding with benzodiazepine receptors (BDR) in the cerebellum of the 10-months-old control rats white the young animals demonstrated only a decrease in Bmax of binding. In 6 months after kindling termination the BDR activity (Bmax) was reduced by one half. However, we think that the increase in Bmax is not responsible for persistence of the increased seizure readiness. It seems possible that down regulation of receptor activity develops independently of kindling but in response to long-lasting corazol application. Probably, Bmax spontaneously decreases after the termination of the long-term corazol application. The single dose of corazol (30 mg/kg) restores the changes in BDR density to the level when seizure readiness has been just fixed (6 months after kindling termination), independently of the primary receptor density.

[The properties of the benzodiazepine receptors in the rat cerebellum after acute seizures and the development of korazol-induced kindling]. / Svoistva benzodiazepinovykh retseptorov mozzhechka krys posle ostrykh sudorog i razvitiia korazolovogo kindlinga.

The acute korazol (pentylenetetrazol) injection (50 mg/kg) induced seizures which were accompanied by a long-lasting (from 30 minutes to 3 days) decrease in benzodiazepine receptor (BDR) density (Bmax) in rat cerebellum without change in affinity. The density of the BDR was normalized on the 7th day after seizure termination. There were no differences in the initial BDR characteristics between the animals more sensitive to korazol (a dose of 25 mg/kg was sufficient for seizure induction) and less sensitive (30 mg/kg were ineffective). The chronic daily (for 24 days) administration of korazol in a subconvulsive dose led to an increase in seizure readiness (kindling). In 30 min after the last korazol injection the BDR density was decreased to the same extent as after the acute 50 mg/kg korasol administration. The BDR density was normalized on the 7th day after kindling. It was demonstrated that the high-dose-induced and after-kindling seizures were underlain by the same mechanisms. The results suggest that the development of kindling depends on the state of the long-lasting receptors rather than the development of kindling forms the long-lasting reactions. The process of summation is at the basis of kindling development. The long-lasting decrease in activity of BDR receptors induced by a subconvulsive dose of korazol is summed with the following effect of the same dose.

[Effects of prenatal exposure to alcohol on the binding of H3-diazepam to the synaptic membranes of the cerebral hemisphere cortex at various stages of ontogenesis in the rat offspring]. / Vliianie prenatal'nogo vozdeistviia alkogolia na sviazyvanie 3H-diazepama s sinapticheskimi membranami kory bol'shikh polucharii mozga na raznykh stadiiakh ontogeneza potomstva krys.

Exposure to ethanol during pregnancy results in the alteration of (3H)-diazepam binding to synaptosomal neocortical membranes from the rat offspring. In male rats, 14 days of age, binding level diminished to 11%. In two-month-old control rats Scatchard plot was biphasic. It has been shown that prenatal exposure to ethanol leads to changes in the nature of binding in two-month-old experimental animals, as compared with the control ones. Possible relationship is discussed between the brain benzodiazepine system disorders and behaviour.

[Effect of intrauterine exposure to ethanol on synthesis of various phospholipids in the rat brain during the postnatal period]. / Vliianie vnutriutrobnogo vozdeistviia étanola na sintez nekotorykh fosfolipidov mozga krys v postnatal'nom periode.

Male rats, whose mothers were given ethanol during pregnancy, were injected inorganic P32 into lateral brain ventricles. Some animals during 1 hour before decapitation were subjected to stress. Phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine were isolated from neocortex and hippocamp. Prenatal alcohol treatment led to 30% inorganic P32 incorporation increase into neocortex phosphatidylcholine. Stress was followed by phosphatidylcholine synthesis level decrease in neocortex by 13% and in hippocamp by 26%. Amplitude of phospholipid synthesis alterations increased after both prenatal alcohol treatment and stress. The results show that prenatal alcohol treatment results in essential disfunction of brain phospholipids synthesis.

[The characteristics of [3H]muscimol binding to the synaptic membranes of the cerebral cortex in the progeny of rats subjected to deprivation of the paradoxical sleep phase during pregnancy]. / Osobennosti sviazyvaniia [3H]mustsimola s sinapticheskimi membranami kory bol'shikh polusharii mozga u potomstva krys, podvergavshikhsia deprivatsii paradoksal'noi fazy sna vo beremennosti.

White rats were subjected to REM-sleep deprivation during 14-20 days of pregnancy. [3H]muscimol binding level of neocortex synaptosomal membranes was significantly higher in their offsprings as compared with the control ones. Possible ways of GABA-ergic system malformations are discussed.

[Effect of intrauterine ethanol exposure on higher nervous activity and on protein and lipid metabolic indices of the brain in rats]. / Vliianie vnutriutrobnogo vozdeistviia étanola na vysshuiu nervnuiu deiatel'nost' i nekotorye pokazateli metabolizma belkov i lipidov mozga u krys.

It has been shown that intrauterine effect of ethanol causes alterations of protein phosphorylation, glycoprotein and lipid synthesis in rat brain in late ontogenesis. These alterations correlated with disordered learning and maintenance of the conditioned reflexes.

[Peculiarities of H3-muscimol binding to neocortex membranes of rats exposed to the effects of ethanol in the prenatal period]. / Osobennosti sviazyvaniia 3H-mustsimola membranami neokorteksa krys, perenesshikh vozdeistvie étanola v prenatal'nom periode.

White rats were subjected to ethanol exposure during 5-20 days of pregnancy. 3H-muscimol binding with synaptosomal neocortex membranes yielded from two month age offsprings was studied. 3H-muscimol binding level for experimental animals was 27% more than for control ones. Possible ways of GABAergic system malformation are discussed.

[Binding of 3H-diazepam by cerebral cortex synaptic membranes in the rat during conditioned reflex elaboration]. / Sviazyvanie 3H-diazepama sinapticheskimi membranami kory bol'shikh polusharii golovnogo mozga krys pri vyrabotke uslovnogo refleksa.

In-vitro experiments were made to compare specific binding of 3H-diazepam with synaptic membranes obtained from the large hemispheres of rats trained the defense conditioned reflex to that in rats exposed to non-combined stimuli (active control). Within the concentration range of 0.37 nM-30 nM, specific binding of 3H-diazepam with the synaptic membranes obtained from the brain of active control animals was considerably higher than that with the synaptic membranes obtained from the trained animals brain.