The effect of DMCM and diazepam on the behavior of rats subjected to ethanol exposure in the prenatal period]

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.     

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

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.     

The characteristics of a change in the congenital and acquired forms of behavior in rats with genetic catalepsy

In two groups of rats--outbred control rats and GC line ones the behaviour in the open field was studied, as well as alimentary situational instrumental conditioned reflex was elaborated. Rats of GC line were less mobile in the open field as compared with the control ones; their investigating reflex was low; several parameters showed a higher level of agitation and fear. Handling of rats of GC line improves these behavioural parameters and brings them closer to the norm. Elaboration of alimentary situational conditioned reflex in rats of GC line is delayed as compared with the control ones. Passive-defensive reflex expressed in the form of cataleptic stupor, is of dominant character and significantly prevails over cognitive and alimentary reflexes.     

Level of neuroactive steroids in the brain and sex-related peculiarities of formation and extinction of conditioned reflex in rats

Sex-related peculiarities of dynamics of brain sex steroids in the process of learning and extinction of the conditioned reflex of passive avoidance have been studied in model experiment. Prior to learning of the conditioned reflex, female rats were found to be distinguished by manifestation of anxiety and fear as compared with male rats. At formation of the conditioned reflex, no significant sex-related differences were detected between males and females, whereas extinction of the conditioned reaction of passive avoidance in males occurred by 2–3 days faster than in females. At learning of conditioned reaction of passive avoidance, in sexually mature male rats there was revealed an increase of the testosterone content in various brain structures, especially in hippocampus and frontal cortex, while its level in blood plasma remained unchanged. Also shown was an elevation of estradiol concentration in female amygdale, whereas at extinction of the conditioned reaction of passive avoidance, a rise of estradiol values was noted in hippocampus and cingular cortex. At the same time, the testosterone level in blood plasma did not change, whereas after extinction of the conditioned reflex the estradiol concentration decreased statistically significantly. Different dynamics of changes of the sex steroid levels in brain and blood plasma can indicate a possibility of their formation in the nervous tissue. The performed correlation analysis confirms the concept of selective involvement of testosterone and estradiol of individual brain structures in realization of processes of learning and memory in sexually mature male and female rats.     

Effect of microinjections of a selective blocker of M1-muscarinic receptors pirenzepine into the neostriatum on the rat motor activity

In simulated discrimination conditioned reflex of active avoidance (CRAA) in T-maze, the effect of bilateral microinjections of the muscarinic receptor M1 selective blocker pirenzepine on the CRAA formation and behaviour in the "open filed" test, was studied in rats. A sharp worsening of the CRAA learning and a significant increase in the motor activity were shown to occur in rats following the microinjections as compared with control rats. The change in the motor responses seems to account for the worsening of the CRAA learning. Another reason of the phenomenon could involve a disorder in perception of conditioned signals and their poor differentiation. The data obtained and the literature data suggest a complex character of changes induced by the blockade of the M1 muscarinic receptors of the neostriatum.     

Level of neuroactive steroids in the brain, and gender-related differences in formation and decrease of conditioned reflex in rats

We investigated gender-related differences in dynamics of the brain sexual steroids during learning and the decrease of conditioned reflex in the modeling experiment. It was revealed that, before training to conditioned reflexes, females manifested a greater anxiety than males. Significant differences between males and females in formation of the conditioned reflex of passive avoidance were not revealed, whereas the conditioned response decrease were by 2-3 days faster in male rats than in females. It was revealed that there was an increase of testosterone content in various structures of the brain, especially in hippocampus and frontal cortex with its constant level in the blood plasma in learning conditioned response of passive avoidance in male adult rats. Also an increased estradiol concentration was found in females' amygdale, while increased value of estradiol was detected in hippocampus and the singular cortex in decrease of the conditioned response of passive avoidance. In blood plasma, the testosterone level was not changed, and the estradiol concentration was reduced significantly after the decreased conditioned reflex. Different dynamics of changes in the levels of sex steroids in the brain and the blood plasma can indicate a probability of their formation in nervous tissue. The correlation analysis confirms the conception about selective involvement of the brain's testosterone and estradiol in the specific structures in realization ofthe learning and memory processes in adult male and female rats.     

Effect of adaptation to central highlands conditions on active avoidance conditioning and its retention after emotional pain stress

The generation of conditioned reflex of active avoidance (CRAA) and its retention after emotional stress were studied in different groups of rats. The degree of conditioned reflex of active avoidance in pre-adapted rats was higher than in non-adapted animals. However, the degree of CRAA maintenance was independent of the character of CRAA fixation and the rats' adaptability after 1 and 3 exposures to emotional stress. In a usual degree of conditioned reflex fixation its maintenance was higher in rats living on the plain than in low-mountain rats (adapted and non-adapted).     

The influence of ZnCl2 injected into the neostriatum on locomotor behavior of rats

The influence of two-week daily microinjections of ZnCl2 into the rostral region of neostriatum on the locomotor behavior of Wistar rats in chronic experiments was studied. The 1-mcg dose of ZnCl2 decreased spontaneous locomotor activity in the "open field" and, beginning with the 5th day of microinjections, inhibited a shuttle-box conditioned avoidance reflex. The reflex recovered only in the first week after the injection withdrawal. The 0.1-mcg dose of ZnCl2 to a lesser extent affected the parameters of conditioned avoidance, whereas the level of spontaneous locomotor activity in this group of animals increased. The observed changes in rat behavior may be associated with the concentration-dependent influence of zinc ions on the ion channels in the membranes of neostriatum neurons, including glutamate activated. The possibility to control the activity of ion channels in a chronic behavioral experiment by zinc ion concentration is discussed.     

The behavioral characteristics of rats selected for their learning capacity]

Experiments were conducted in rat strains selected for high (KHA) and low (KLA) levels of the elaboration of conditioned reflex of active avoidance in shuttle box. KHA rats, as compared with the KLA ones, showed considerably higher indices of learning the shuttle avoidance, a greater number of intersignal runs during learning, a higher level of motor activity under open field conditions and its more marked extinction. These data point at the role of both associative and non-associative processes in the formation of active avoidance reflex. During 5 days of reflex training the rats of both strains retained a high level of defecation until the end of the test that pointed at the emotional strain unceasing in spite of the automatization of the reflex.     

Effect of adaptation to altitude hypoxia in early ontogeny on the indices of higher nervous activity]

Newborn male and female Wistar rats were adapted to hypoxia in a pressure chamber. Adaptation was started from the "altitude" of 1000 m, 1 hour daily, and then the time and the intensity of hypoxic actions were gradually increased: beginning from the 17th day the animals were subjected to adaptation to the "altitude" of 5000 m, for 5 hours, 5 days a week. The defence conditioned reflex of active avoidance was provoked in the animals after 2-month adaptation. A tendency to a more rapid elaboration of the reflex and a markedly enhanced degree of its retention in comparison with control was revealed in the adapted males. No significant changes in the elaboration and rentention of the reflex were found in the female animals adapted to hypoxia under analogous conditions.     

The characteristics of shuttle avoidance learning in spontaneously hypertensive and normotensive rats]

In spontaneously hypertensive (strain SHR) and normotensive (strain WKY) rats was studied the elaboration of conditioned reflex of active avoidance in shuttle box. In case when the shuttle box was divided by a partition the SHR rats learned worse than WKY rats. In shuttle chamber without partition the SHR rats, on the contrary, learned better that WKY ones. Such character of interlinear differences can be connected with properties of formation of the instrumental habit of deliverance from electropainful stimulus, because the presence of partition significantly hampered its fulfillment. The obtained results, compared with literature data, testify to the fact that differences of SHR and WKY rats in elaboration of conditioned reflexes are explained basically by the properties of their unconditioned activity and not of the associative processes.     

Prediction of the severity of damage and disruption of work ability in reaction of the body to alcohol load prior to radiation exposure in the superlethal range

In experiments on 121 white non-linear rats, 44 Papio hamadryas and 29 Macaca fascicularis, animals' reactions on the alcohol impact (AI) and following exposure to supralethal doses were compared. The animals were intravenously injected with 5% ethanol in the glucose solution, 2.1 g/kg for rats and 0.46-0.51 g/kg for monkeys. Monkeys' response to AI was scored in four-point scale by estimating of abnormalities in motor activity, coordination of motion and changes in conditioned reflex activity. It was shown that changes in the ability of alcohol-injected rats to perform the learnt exercises in the "jump box" could be used for prediction of their response to the exposure to supralethal doses of ionizing radiation. Observing the AI-response in monkeys along with a method "function of spying for moving object" made possible to predict not only a general degree of loss of working ability but also to estimate individual impairments of spying functions. In 65% monkeys high similarity of the reactions to AI and ionizing radiation was observed.     

Electroencephalographic studies on classically conditioned defensive reflex and avoidance lever-pressing in the dog (author's transl)]

Six dogs with implanted cortical and subcortical electrodes were trained to press a lever to avoid electroshock to a hind leg. Intracerebral stimulation at low frequency was delivered as an "indifferent" or a "CD" tracer. Changes of EEG responses to the tracers prior to the voluntary lever-pressing or the conditioned avoidance lever-pressing were prior to the voluntary lever-pressing or the conditioned avoidance lever-pressing were examined by continuous frequency analysis. (1) Evoked potentials to the tracer stimulation were changed just before the conditioned defensive reflex, the voluntary lever-pressing and the conditioned avoidance lever-pressing, regardless of the site of the tracer stimulation. (2) The cortical and subcortical structures (Hippo, RF) seemed to be involved in the neural circuit responsible for the avoidance lever-pressing, whereas the sensorimotor cortex may be essential in the circuit for the alimentary lever-pressing. (3) The avoidance lever-pressing and the EEG response to the "CS" tracer were influenced by the internal inhibition (experimental extinction, inhibitory mechanism was discussed.     

Participation of the genetic apparatus of the hippocampal and neocortical cells in the mechanisms of action of desglycine-arginine vasopressin on learning and memory processes in rats

The paper deals with the influence of synthetic vasopressin analogue--desglycine-arginine vasopressin (DG-AVP) on the content of RNA and fractional composition of chromatin proteins in the tissue of neocortex and hippocampus of intact white rats and after establishing of two-way avoidance reflex. Administration of the peptide alone significantly increased RNA content in hippocampal tissue, injection of the peptide 10 min before conditioning did not lead to significant changes in RNA quantity as compared to that in animals in which the conditioned reflex was established against the background of saline administration. In neocortical tissue neither learning itself nor administration of DG-AVP alone was accompanied by significant changes in RNA content, while learning against the background of peptide injection significantly increased RNA in that structure. In hippocampal and neocortical tissues quantitative changes were observed in certain fractions of chromatin proteins in all animal groups studied.     

Changes in brain serotonin metabolism and [3H]-serotonin receptor binding during recall of conditioned passive avoidance in rats

The content of serotonin and its metabolite 5-hydroxyindoleacetic acid, monoamine oxidase activity, and [3H]-serotonin radioligand receptor binding were examined in the prefrontal cortex, striatum, amygdala, hippocampus and periaqueductal gray matter at different time after one-trial passive avoidance training of rats. Changes in the serotonergic activity were observed only in rats, which showed retrieval of conditioned passive avoidance response. No serotonergic changes were found immediately and one day after training. Also, there were no changes in trained rats without retrieval of conditioned passive avoidance response or rats with experimental amnesia. The pattern of the involvement of brain structures in the retrieval process was also revealed. [3H]-serotonin binding was decreased in the amygdala, periaqueductal gray matter and striatum, whereas it did not change in the prefrontal cortex and hippocampus. At the same time, the serotonin content in these structures did not differ from that of intact rats. Deamination of serotonin by monoamine oxidase and active transport of 5-hydroxyindoleacetic acid from nerve terminals were increased in the amygdala and periaqueductal gray matter, whereas in the striatum serotonin catabolism was decreased. The obtained differences in serotonin catabo- lism suggest that the decrease in receptor binding of serotonin in these brain structures is provided by different synaptic processes: presynaptic changes in the striatum and postsynaptic receptor changes in the amygdala and periaqueductal gray matter. It is concluded that the decrease in the serotonergic activity in the amygdala and periaqueductal gray matter represents one of the mechanisms activating the emotiogenic system mediating the memory trace retrieval in inhibitory avoidance learning.     

Effect of cadmium chloride on the processes of learning and memory in rats

Intraperitoneal injection of cadmium chloride (4 mg/kg) to rats before elaboration or reproduction of two-way avoidance conditioned reflex (TACR) disturbs both these processes. Deterioration of elaboration does not affect connections fixation and their subsequent reproduction. Injection of the substance before the elaboration of passive avoidance conditioned reflex (PACR) depresses elaboration and consolidation. Injection of cadmium chloride before testing of PACR preservation does not influence the processes of engrams reproduction. The observed disturbances cannot be connected with changes of animals motor activity.     

The long-term effect of acute hypoxic hypoxia on shuttlebox avoidance learning in rats

Long-term influence was studied of the acute hypoxic hypoxia seance on rats behaviour in situation of elaboration of the conditioned reaction of active avoidance of electric shocks in shuttle chamber. It was found that in 2.5-3 months after the hypoxia seance, the experimental animals significantly differed from the intact controls by dynamics of CR elaboration (rats which had hypoxia were ahead of the control ones) and by distribution of the conditioned reactions latencies (for experimental animals this distribution was shifted to minor values). The character of these behavioural shifts coincided with that observed in the group of rats with local unilateral hippocampus lesion. The obtained results and numerous data presented in literature on the influence of the hippocampus lesion on animals shuttle avoidance learning, allow to conclude that the seance of hypoxic hypoxia leads to the disturbance of the hippocampus function. This conclusion conforms to the data on diffusive death of the hippocampal and neocortical neurones as a result of hypoxia action.     

Behavioral and biochemical characteristics of rats preferring ethanol or water

A study was made of the RNA biosynthesis intensity in the brain cortex depending on the rate of the learning of the conditioned active avoidance and food reinforcement alteration responses in ethanol or water preferring rats placed in a complex maze. The level of the brain RNA biosynthesis in ethanol preferring rats was lower as compared with that in rats preferring water. In ethanol preferring rats, the rate of the learning of the conditioned active avoidance response was lower, whereas that of the learning of the alternation response was greater than in water preferring rats. The data are discussed in accordance with the concepts that disorders in the interaction of transmitter and genetic structures of brain cells form the basis of the behavior of ethanol preferring animals.     

Conditional Reflex Reaction of the Passive Avoidance in Female and Male Rats Exposed to Hypoxia at Different Terms of Prenatal Development

Elaboration of the conditional reflex reaction of passive avoidance was studied in the 42–46-day old offsprings of two groups of female rats: intact (control) and exposed to action of hypoxia at the 13th, 16th or 19th day of pregnancy. The parameter of learning was the time of stay of the rats in a dark camera, in which they obtained an electroshock. It is shown that the prenatal hypoxia has different effect on the ability to elaborate the conditional reflex reaction of passive avoidance in female and male rats. By this parameter, no differences were revealed in the male group between the control and the animals exposed to hypoxia at different terms of intrauterine development. In female exposed to hypoxia at the 19th day of gestation, it was not possible to elaborate the conditional reflex reaction of passive avoidance. In females exposed to hypoxia at the 13th day of gestation the parameters of learning were lower, whereas in the females exposed to hypoxia at the 16th gestation day they were higher than in control animals.     

Peculiarities of H3-muscimol binding to neocortex membranes of rats exposed to the effects of ethanol in the prenatal period

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.