Interaction of myelin basic protein and 2',3'-cyclic nucleotide phosphodiesterase with mitochondria.

The content and distribution of myelin basic protein (MBP) isoforms (17 and 21.5 kDa) as well as 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) were determined in mitochondrial fractions (myelin fraction, synaptic and nonsynaptic mitochondria) obtained after separation of brain mitochondria by Percoll density gradient. All the fractions could accumulate calcium, maintain membrane potential, and initiate the opening of the permeability transition pore (mPTP) in response to calcium overloading. Native mitochondria and structural contacts between membranes of myelin and mitochondria were found in the myelin fraction associated with brain mitochondria. Using Western blot, it was shown that addition of myelin fraction associated with brain mitochondria to the suspension of liver mitochondria can lead to binding of CNPase and MBP, present in the fraction with liver mitochondria under the conditions of both closed and opened mPTP. However, induction of mPTP opening in liver mitochondria was prevented in the presence of myelin fraction associated with brain mitochondria (Ca2+ release rate was decreased 1.5-fold, calcium retention time was doubled, and swelling amplitude was 2.8-fold reduced). These results indicate possible protective properties of MBP and CNPase.

[Evolution of dissociative learning].

This review considers data obtained during the entire research period of state-dependent learning. Understanding of this phenomenon has significantly evolved during the past decades, as a result of the increasing amount of facts revealed while studying state-dependent learning. Consequently, a situation has arisen where different papers may describe same phenomena using different terms. This does not promote understanding of the described phenomena. Therefore a need for a paper emerged, that would analyze the evolution of state-dependent learning and would offer terminology corresponding to all the data collected on the subject.

Dissociated learning using GABAergic drugs.

Experiments on Wistar rats addressed the possibility of dissociated learning using drugs acting directly on brain GABA(B) receptors. A previously suggested hypothesis was tested: that the cholinergic system of the brain plays the decisive role in the mechanisms of dissociative learning. The data obtained here provided evidence that dissociated learning an occur with compounds acting on the GABAergic transmitter system of the brain. Dissociated states arose on treatment of animals with both the GABA-mimetic baclofen and the GABA receptor antagonist 5-aminovaleric acid. Thus, these results show that dissociated learning can occur using drugs acting on both the cholinergic and the GABAergic transmitter systems of the brain.

[Dissociated learning with GABAergic drugs].

The possibility of dissociated learning was investigated using drugs which act directly on GABAB receptors of the brain. The earlier proposed suggestion that the cholinergic system plays a key role in the mechanisms of dissociated learning was tested. It was shown in male Wistar rats that dissociated learning was possible with GABAergic drugs. The dissociated state was induced by injecting the animals with both GABA agonist Baclofen and GABA antagonist 5-aminovaleric acid. Thus, dissociated learning is possible with drugs which act on either cholinergic or GABAergic transmitter systems.

[Complex perception of stimuli during conditioning]. / Kompleksnoe vospriiatie razdrazhitelei v protsesse vyrabotki uslovnykh refleksov.

The review concerns the effects of a variety of stimuli on the reproduction of conditioned reflexes. By the literature data, during conditioning of any type, besides the single stimulus intentionally applied by an experimenter as a conditioned one, an animal perceives the whole complex of stimuli (acoustic, visual, olfactory, algesic, and other exteroceptive, proprioceptive, and interoceptive stimuli), including those of the environment and time of the day during training. Many of these stimuli are essential for the reproduction of the acquired habit. The complex of stimuli that act on an animal during the reproduction should in all parameters correspond to that perceived by the animal during training. If the complexes differ at least in one stimulus, the reproduction of the reflex may fail.

[The use of dissociated learning in the study of the mechanisms of memory]. / Ispol'zovanie dissotsiirovannogo obucheniia pri issledovanii mekhanizmov pamiati.

The review is dedicated to description of the phenomenon of dissociated learning. The distinct criteria which discriminate this phenomenon from those similar in appearance are presented. The experimental procedure is described: habituation of an animal, a device for dissociated learning, and the mode of determination of the necessary dose of a drug and injection time. Different versions of dissociated learning which can be gained using the same device, as well as methodical recommendations for researchers in the field of studying this phenomenon. Analysis of the author's data shows that the use of dissociated learning can be promising for studying mechanisms of learning and memory.

Studies of the role of the brain cholinergic system in the mechanisms of dissociative learning.

Rats were trained to make conditioned food reflex excursions in two states: in normal conditions and on a background of treatment with pharmacological agents producing dissociative states. A number of cholinergic substances were completely interchangeable in dissociative learning; anticholinergic compounds efficiently neutralized the ability of cholinergic substances to produce dissociative states; muscarinic cholinoreceptors played the leading role in production of the dissociative state.

[The role of the cholinergic system of the brain in the mechanisms of dissociated learning]. / Issledovanie roli kholinergicheskoi sistemy mozga v mekhanizmakh dissotsiirovannogo obucheniia.

The mechanisms of dissociated learning in rats were studied with application on conditioning technique and pharmacological analysis of memory. Anticholinesterase drugs were shown to be interchangeable in inducing dissociated states in learning. Anticholinergic substances completely neutralized the ability of cholinergic drugs that create dissociated states. It was shown that muscarinic cholinergic receptors largely contribute in inducing dissociated states. The findings well agree with the earlier author's hypothesis that the cholinergic brain system plays a decisive role in the mechanisms of dissociated learning.

[Ability of reversible cholinesterase inhibitors to support dissociative learning]. / Issledovanie sposobnosti obratimykh ingibitorov kholinésterazy obespechivat' dissotsiirovannoe obuchenie krys.

In the experiments on rats performed to study dissociated learning it was found that reversible inhibitors of cholinesterase are interchangeable. It was shown that neutralization of the behavioral effect of cholinesterase inhibitors may be induced most successfully by combined administration of M- and N-cholinergic blocking agents.

[Development of a dissociated state in the rat after administration of carbacholine into the hippocampus]. / Vozniknovenie dissotsiirovannogo sostoianiia u krys pri vvedenii k karbakholina v gippokamp.

Food-procuring conditioned reaction was elaborated in rats. A single injection of carbacholine into the dorsal area of the hippocampus elicited prolonged (for several days) stable amnesia, during which elaboration of a second habit in the same animals proved possible. After cessation of the agent action, the initially elaborated conditioned reaction recurred. The obtained results allow to interpret the amnesia elicited by injection of carbacholine into the hippocampus as a dissociated state.

[Role of the cholinergic and monoaminergic systems of the brain in dissociated learning]. / Rol' kholinergicheskoi i monoaminergicheskikh sistem mozga v dissotsiirovannom obuchenii.

Rats placed in an experimental chamber, were trained to perform two dissociated reactions; the one--in a normal state, the other--after administration of physostigmine. Then the animals were divided into 10 groups and in each group the performance of the elaborated conditioned reflexes was tested after administration of the substances influencing cholinergic and monoaminergic brain systems. It is shown that the dissociation state after physostigmine administration is due to the influence of this substance on the cholinergic brain system. The increase of biogenic amines content in the central nervous system leads to the appearance of dissociation after a smaller dose of anticholinesterase. This seems to reflect a modulating influence of monoaminergic brain systems on the cholinergic system during performance of the dissociated reactions.

[The effect of iproniazid on biogenic amine levels, elaboration and reproduction of alimentary conditioned reflexes]. / Vliianie iproniazida na uroven' biogennykh aminov, vyrabotku i vosproizvedenie pishchevykh uslovnykh refleksov

A study of the action of iproniaside on alimentary conditioning has shown that even its small doses (25 mg/kg) disturb the formation of the conditioned reaction, while large doses (200-250 mg/kg) do not disturb the reproduction of the conditioned reaction elaborated and stabilized before the administration of the drug. Hence, dissociated learning with the use of iproniaside is impossible. The applied doses of iproniaside result in an increased level of biogenic amines in the dopaminergic nigro-neostriate and reticulo-septal brain systems. It is therefore assumed that the effects of iproniaside on learning are due to its influence on the level of the CNS biogenic amines.