[Modern approaches to human cognitive activity enhancement].

Recent literature on human cognitive activity enhancement is reviewed and summarized. Two classes of pharmacological approaches are picked out, i.e. modern aspects of traditional substance utilization and application of specially developed drugs. Among non-pharmacological approaches a number of psychological, physiological, behavioral and biophysical methods to improve human cognition, memory and learning are analyzed. The most attention is paid to non-drug approaches that utilize bioelectric processes of the individual including characteristics of its brain electrical activity--electroencephalogram (EEG) to enhance different aspects of cognitive functioning. Some promising lines of these investigations are delineated.

[Comparative analysis of the effects of estrogens and tamoxifen on the brain higher functions].

At present, it is commonly accepted that estrogens modulate both cognitive and psycho-emotional status. Induced or natural hypoestrogeny is frequently accompanied by a complex of pathological states including suppressed state, anxiety, and weeping, sometimes with the development of depression. It is established that a substituting hormonal therapy in some cases favors restoration of the cognitive function and provides correction of affective disorders. Unfortunately, this therapy is accompanied by side effects and has some counterindications, which restricts its use in clinical practice. For this reason, it is of interest to try alternative agonists/antagonists of estrogen receptors possessing selective activity with respect to estrogen-sensitive tissues (including CNS), but these agents are still insufficiently studied. The given review describes the effect of estrogens on the brain functions, considers the mechanisms of action, and analyzes undesired side effects accompanying long-term administration. In particular, the results obtained in recent years concerning the effect of tamoxifen on the brain functions are summarized.

Some psychosomatic causal factors of restraint-in-water stress ulcers.

Rats were stressed by 75 min restraint in a tube suspended vertically while dry (19 degrees C) or partially immersed in tanks of water at different temperatures (19, 27, 35 degrees C), either in a conscious state or while under pentobarbital anesthesia. Restraint was followed by 75 min rest in the home cage and then sacrificed under halothane anesthesia. Assessment of the degree of gastric erosion indicated that restraint alone, whether the animal was rendered unconscious or not, was not sufficient to induce ulceration. However, in conscious animals, the addition of partial immersion did induce ulceration that was inversely related to the temperature of the water bath. This effect was not merely the result of brain stem and spinal reflex processes, because unconscious animals exposed to the most severe conditions (19 degrees C) showed no ulceration.

The effects of vasopressin on memory processes in Java monkeys.

The roles of vasopressin (arginine-vasopressin) in controlling conditioned operant food-procuring reflexes and various types of memory were studied in monkeys. Types of memory were: conditioned reflex, image (Hunter-Kerr test), short-term, and long-term. The effects of vasopressin were assessed in terms of objective measures of higher nervous activity: movement and autonomous functions. These studies showed that administration of vasopressin to monkeys had different effects on simple operant food-procuring responses and memory processes. Vasopressin had greater effects on memory processes and the restoration of memory after functional derangements of higher nervous activity. The question of the formation of the two types of effect of vasopressin on higher nervous activity is discussed in relation to the evolution of mammals.

Effects of verapamil and nifedipine on psychomotor performance in human subjects.

The present study was undertaken to evaluate the effects of two structurally dissimilar calcium channel blockers, verapamil (a phenylalkylamine) in a single dose of 40 and 80 mg, and nifedipine (a dihydropyridine) in a single dose of 10 and 15 mg, on psychomotor performance and higher mental functions in human volunteers. Placebo and diazepam (5 mg) were used as negative and positive controls respectively. For evaluating these functions, tests employed were arithmetic ability, visual and auditory reaction time, letter (alphabet) cancellation, rapid fire arithmetic deviation and short term memory for playing cards. Careful record was kept of the heart rate, blood pressure and side effects of the therapy, each time the psychomotor tests were performed. Verapamil, both in 40 and 80 mg dose, was found to impair the performance of subjects to a significant extent in auditory reaction time, letter cancellation and short term memory. These effects were similar to those observed with administration of diazepam. With nifedipine, impairment in performance was observed only in rapid arithmetic deviation test. Thus, calcium channel antagonists, specially verapamil, impaired psychomotor performance of human subjects in our study.

[Adaptogenic role of serotonin in dogs coming out of an experimental neurosis]. / Adaptogennoe znachenie serotonina u sobak pri vykhode iz éksperimental'nogo nevroza.

In a study carried out on dogs by means of alimentary salivary conditioned reflexes, it was found out that serotonin injection into the anterior limbic cortex and the action of neurogenous stimuli lead neither to the development of experimental neurosis nor to the usual for the neurosis increase of blood serotonin level. At the treatment of experimental neurosis by small doses of 5-oxytryptophan, the therapeutic effect of this serotonin predecessor appeared only in the days of its injection. In the subsequent period, the neurotic changes in the higher nervous activity continued, and the blood serotonin level remained increased. These data as well as materials earlier obtained on the increase of the blood serotonin level at neurosis in dogs, give reason to consider the increase of activity of the serotoninergic system at neurosis as one of adaptogenous factors contributing to the coming out of neurosis.

[The effect of neuropeptides on the processes of higher nervous activity in primates. The action of cyclic analogs of enkephalins on the behavior of lower monkeys]. / Vliianie neiropeptidov na protsessy vysshei nervnoi deiatel'nosti u primatov. Deistvie tsiklicheskikh analogov énkefalinov na povedenie nizshikh obez'ian.

The influence of 2 cyclic enkephaline analogues (IVS-43 and IVS-46) on group and individual behaviour of rhesus and baboon monkeys was studied. The effect of IVS-46 on competitive and operant goal-directed behaviour of the monkeys was expressed. Possible mechanisms of functional reorganization of the higher nervous activity of primates under the influence of neuropeptides are discussed.

[Neuromediator shifts in the peripheral blood of dogs resulting from negative emotiogenic exposure]. / Neiromediatornye sdvigi v perifericheskoi krovi sobak vsledstvie otritsatel'nogo émotsiogennogo vozdeistviia.

The analysis of negative emotiogenic influence in dogs carried out according to dynamics of levels of acetylcholine and catecholamine content in peripheral blood and concomitant changes of the higher nervous activity, allows to conclude about the participation of both cholinergic and catecholaminergic neurotransmitter systems in reactions to this influence with a relative predominance of the first one. In animals with decreased reactivity and with compensatory abilities of the cholinergic system, the same influence leads to enhancement of the specific significance of the reaction of the catecholaminergic system, and especially of its transmitter, noradrenergic component.

[A computer ethological-pharmacological analysis of the intraspecific behavior of primates]. / Komp'iuternyi étologo-farmakologicheskii analiz vnutrividnogo povedeniia primatov.

Experiments were performed on primates (Cercopithecus sabeus, Macaca maurus, Cebus apella). Possibility to formalize the structure of normal and pathological monkey behaviour was shown by computerized technique. Rigid dominant-subordinate structures (linear type) were demonstrated on Macaca maurus, Cercopithecus sabeus, Cebus apella. These structures display some variants of normal relationship between monkeys. Raising in isolation from conspecifics determines behavioural disadaptation and pathological behaviour, e.g. "timid-defensive" syndrome. Model of "timid-defensive" syndrome in isolated primates seems to be useful for psycho-pharmacological research, for assessment of anxiolytic and antidepressive properties of drugs.

[Conditioned reflex activity and several vegetative reactions in dogs during the recovery period following repeated reanimation]. / Uslovnoreflektornaia deiatel'nost' i nekotorye vegetativnye reaktsii sobak v vosstanovitel'nom periode posle povtornoi reanimatsii

Conditioned activity and vegetative reactions were studied in dogs which repeatedly underwent clinical death from electrical trauma and were reanimated by donor artificial blood circulation. (The first clinical death was provoked 15 to 18 months prior to the repeated death and was caused by drowning and blood loss). On the first few days after reanimation the functions of the higher parts of the CNS and the vegetative nervous system were considerably disturbed. This was manifested in diminished effector reactions to conditioned stimuli, in narcotic and ultraparadoxal phases in conditioned activity, in tachycardia and a higher respiratory rate. The disturbances gradually diminished and by the 5th to 13th day following reanimation completely disappeared. The nature and depth of the disturbances correlated with the basic properties of the animals' type of higher nervous activity. The conditioned reactions were restored despite the retained pronounced dystrophic and destructive changes in the cerebral cortex. This is significant proof of important compensatory capacity for conditioned activity in dogs.

[Changes in the ultrastructure of the cerebral cortex in rats during learning and in disorders of higher nervous activity]. / Izmeneniia ul'trastruktury kory bol'shikh polusharii u krys v protsesse obucheniia i pri narushenii vysshei nervnoi deiatel'nosti

The results are outlined of a complex study of the ultrastructure of the rat cerebral cortex after learning and higher nervous activity disturbance. In the case of learning with preliminary stimulation with al-amphetamine or without it, the subcortical processes in the motor and auditory analysers of the cerebral cortex are characterized by sharp structural-functional activation of the apparatus of energy supply, of protein synthesis and of the synaptic zones. The length of the synaptic active zones increases, and extensive development of spine apparatuses is recorded in the postsynaptic area in the form of intricate membrane complexes. Quite the contrary, in cases of higher nervous activity disturbances, destruction of the organelles and desintegration of spine apparatuses is clearly pronounced. The question of the role of the latter in the memory processes is discussed.

[Changes in the higher nervous activity of the progeny of alcoholized male white rats]. / Izmenenie vysshei nervnoi deiatel'nosti u potomstva alkogolizirovannykkh samtsov belykh krys.

Some forms of behaviour of the offsprings of male rats, which within a period more than 1 month gave preference to 20% ethanol solution over water (I group), were compared with behaviour of the offsprings of males, in which alcoholic motivation had been interrupted after a period of preferential consumption of ethanol during 1 month (II group), and behaviour of the offsprings of intact males (III group). Exploratory and locomotor activity in the animals of the I group was lower, and the level of anxiety was higher, than in the animals of the II group; there were no distinctions between the animals of the II and the III groups (by testing in elevated plus-maze). Memory traces in a test of avoidance by swimming retained worse in the females of the I group, than in the females of the II group; there were no distinctions between males. Capability for bilateral active avoidance conditioning was higher in the animals of the I group, but at the same time the number of animals, which demonstrated non-escape reaction, increase. Forced alcoholization of males of the I and the II groups was carried out beginning from the age of 7 months. Within 2.5 months after the beginning of alcoholization 2/3 of the rats of the I group demonstrated ethanol preference during a testing period of 1 month. Such preference retained only in 14.3% of the animals of the II group. It is supposed that the main factor, which determines predisposition of the offsprings to alcohol consumption, is alcohol consumption by parents rather than their own predisposition.

[The reactivity of the hypophyseal-adrenal system in rats with different forms of adaptive behavioral pathology]. / Reaktivnost' gipofiz-adrenalovoi sistemy krys pri raznykh formakh patologii adaptivnogo povedeniia.

The dexamethasone suppression test (DST) was applied to male Wistar rats with different models of depression: group with the learned helplessness, group with informational neurosis provided by time-deficit conditioned avoidance training, as well as groups of rats of two strains selected for low (KLA)--and high (KHA) avoidance learning. The pre-dexamethasone basal and stress-induced corticosterone levels were similar in intact rats and those exposed to inescapable shock. The dexamethasone administration (5 mkg/kg) failed to decrease the serum corticosterone level in rats with learned helplessness. The informational neurosis increased significantly the basal corticosterone level and decreased the stress response. Serum corticosterone levels were similar in KLA and KHA rats. These results give evidence that two stress-induced rat models of depression with similar behavioural disturbances (reduction of escape/avoidance reactions) exhibit marked differences in the activity of hypothalamo-pituitary-adrenal (HPA) axis.

[Individual behavior characteristics of dogs in conflict between the probability and the quality of reinforcement]. / Individual'nye osobennosti povedeniia sobak pri konflikte mezhdu veroiatnost'iu i kachestvom podkrepleniia.

In experiments on dogs with equiprobable right and left reinforcements in the choice of feeder in conditions of free behaviour, direct correlation was found between the strength of the nervous system and the strategy of dogs behaviour. The dogs of strong type, despite the difference in equilibration and lability, manifested one, similar strategy of behaviour with dominating preferences, definite and goal-directed actions; the dogs of the weak type displayed another strategy, characterized by uncertainty, permanent hesitations in choice reaction. In situation of competition of probability and value of reinforcement, some different aspects of animals typology appeared, presumably connected with individual characteristics of functioning of four brain structures as a basis of types of higher nervous activity (frontal cortex, hippocampus, amygdala, hypothalamus). Behaviour of choleric and flegmatic was oriented to a high probability of events and that of sanguinic and melancholic--to a low one. Thus, "informational" and "motivational" factors of behaviour organization are connected with interaction of specialized brain macrostructures, and properties of this interaction become apparent in animals typology.

[The comparative action of relanium and oxytocin on higher nervous activity in lower monkeys]. / Sravnitel'noe deistvie relaniuma i oksitotsina na vysshuiu nervnuiu deiatel'nost' nizshikh obez'ian.

Effects of relanium and oxytocin on higher nervous activity was studied in four rhesus monkeys (Macaca mulatta) and two baboons (Papio hamadryas). During observation of the animals in enclosure tranquilizing effect was seen only after relanium administration. Under the same conditions oxytocin practically did not change the general behaviour pattern of monkeys. However, steady behavioural transformations were observed under the conditions of competitive food-procuring behaviour and during the operant goal-directed reaction. Decreasing aggressiveness of dominants oxytocin in contrast to relanium had no negative effect upon their general motor activity and sensory perception. Differences in effects of the tranquilizer and the peptide were seen also at the unit activity level of the neurons. The first drug lowered the unit activity level and the degree of the functional connections in neuronal populations in a number of cortical structures. Administration of the second one led to selective shifts of the unit activity mainly in the frontal cortex of the monkeys.

[The role of cholinergic mechanisms in memory processes in experimental neurosis in dogs]. / Rol' kholinergicheskikh mekhanizmov v protsessakh pamiati pri éksperimental'nom nevroze u sobak.

In experiments on dogs the role was studied of cholinergic mechanisms in memory processes at different stages of neurosis. Predominance was shown in initial state of M-cholinergic mechanisms which also in conditions of neurotic inhibition of conditioned activity decrease the level of functioning less than N-cholinergic link. In the postneurotic period excessive activity of N-cholinergic memory mechanism was revealed. The supposed mechanisms are discussed of cholinergic system disturbances in neurosis dynamics and possibility of their pharmacological correction.

[A neuropharmacological analysis of individual preference for the probability and quality of reinforcement]. / Neirofarmakologicheskii analiz individual'nogo predpochteniia veroiatnosti i kachestva podkrepleniia.

Under the influence of diazepam in doses of 0.2-2.0 mg/kg in a situation of different probability and value of a reinforcement the dogs--sanguinics and melancholics change their strategy of behavior, from the preference at norm of a reinforcement of the low probability but the better quality to that of the high probability but the worse quality. Under the same conditions the strategy of behaviour of cholerics and phlegmatics practically does not change. The change of behaviour strategy under the influence of diazepam in sanguinics and melancholics is proposed to be connected with a depressing effect of the drug on the hippocampus and amygdala and simultaneous activation of the hypothalamus and the frontal cortex. The data obtained are discussed from the position of P. V. Simonov's concept on the four above-mentioned brain macrostructures as the basis of the type of the higher nervous activity and behaviour of animals and man.

[The effect of vasopressin on memory processes in Macaca fascicularis]. / Vliianie vazopressina na protsessy pamiati u iavanskikh obez'ian.

The role of vasopressin (arginin-vasopressin) in the regulation of conditioned instrumental food-procuring reactions and different kinds of memory such as delayed reflexes, image, short-, and long-time memory was studied in monkeys. Motor and autonomic effects of vasopressin were assessed. It was found that in monkeys, vasopressin administration differently affected the simple conditioned food-procuring reactions and memory. During functional disorders of the higher nervous activity, vasopressin was more efficient in its action on memory and its restoration. Formation of two types of vasopressin effects on the higher nervous activity in evolution of mammals is discussed.

[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 ubiquinone Q10 and biotin on the growth and development of premature animals]. / Vliianie ubikhinona Q10 i biotina na rost i razvitie nedonoshennykh zhivotnykh.

Biotin (0.3 mg/kg per os) and ubiquinone Q10 (50 mg/kg, per os) during chronic administration were found to produce stimulating effects on premature animals. The two drugs contributed to a more rapid development of memory and learning processes in premature new-born rats than in mature ones, normalized the major parameters of carbohydrate and lipid metabolism. Some specific features and differences were ascertained in the stimulating effects of biotin and ubiquinone Q10.