Peculiarities of Neurohormonal Modulation of Memory and Learning Processes in Young and Old Monkeys <Emphasis Type="Italic">Macaca mulatta</Emphasis>

Comparative data are presented about peculiarities of neurohormonal regulation of the memory and learning processes in young and old monkeys Macaca mulatta. It is shown that the hypothalamic neurohormones, vasopressin and thyroliberine, produce on the whole a unidirectional facilitating effect on the inherited and simple forms of the nervous activity in young and old animals. It is established that vasopressin, thyroliberine, and ACTH_4–10 participate differently in regulation and compensation of disturbed higher nervous functions in old monkeys. The compensatory effects of vasopressin are more pronounced at intranasal administration of its ultrasmall (0.01 jg/kg) doses. The thyroliberine administration had the longer and more expressed disinhibition effect on the conditional reflex memory in old monkeys, as compared with young ones. The question is discussed about different effects of vasopressin and thyroliberine on the higher nervous functions in young and old monkeys from the point of view of cytoarchitectonic changes in the neocortex and of immunohistochemical changes in the hypothalamus nuclear structures.     

Role of Neuropeptides in Brain Asymmetry

A brief review is presented of the literature data on peculiarities of functional asymmetry of brain in animals of different phylogenetic level and asymmetry of the nervous, immune, and endocrine systems. There exposed results of chronic experiments on monkeys to study role of opioid neuropeptide, Met-encephalin (ME), and of hypothalamic neurohormones, vasopressin (VP) and thyroliberin (TL), in functional asymmetry of the monkey brain. The experiments are carried out on model of feeding behavior (complex forms of reactions of choice of side of the reinforcement). It is established that TL, VP, and ME participate in regulation of functions of different brain hemispheres. It is shown that effects of the drugs depend on their dose, initial functional state, and dominance of the particular extremity. It is revealed that administration of ME and neurohormones produces different effects on dominance of the left and right hemispheres. The issue of possible application of neuropeptides in clinics to compensate human motor disturbances after brain ischemia is discussed.     

The effect of vasopressin on memory processes in Macaca fascicularis]

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 Neuropeptide Compensation for Impaired Brain Functions in the Ascending Rows of Mammals: Interaction between the Nervous and Immune Systems

The role of opioid neuropeptides and immunization of animals by inoculating conjugates was studied in the comparative rows of mammals (hedgehogs, cats, and monkeys) to consider the possibility of compensating for neurotic disorders of higher nervous activity (HNA). It was found that small doses of -endorphin (15–25 g/kg) and met-enkephalin produce a short-term facilitating effect on HNA. The administration of large doses (50–80 g/kg) aggravates neurosis. Immunization by using the -endorphin conjugate leads to the normalization of impaired brain functions by all HNA indices. Normalization of brain functions is accompanied by the formation of antibodies in blood plasma. The compensatory effects of immunization inoculating the -endorphin conjugate are most manifest and stable (three to four months) in monkeys. The question of the interaction between the nervous and immune systems is discussed in the article.     

Regulatory Effect of Exogenous Vasopressinon Autonomous Functions and Higher Nervous Activity in Hedgehogs Erinateus auritus under Conditions of High Environmental Temperatures

The role of vasopressin (arginine–vasopressin) in animal adaptation to the effect of high environmental temperatures as well as a possibility to prevent development of thermal stress by use of vasopressin was studied under conditions of chronic experiments in hedgehogs. The experiments were carried out on a model of feeding behavior with objective recording of motor and autonomous components of the higher nervous activity and body temperature as well as the basal gas exchange. It is established that exposure of hedgehogs to a heat chamber at 40°C for 35 min is accompanied by a disturbance of autonomous functions and suppression of conditional reflex activity of the brain. The body temperature and oxygen consumption rise considerably on the background of the heat exposure. A preliminary injection of vasopressin at low dosages was found to prevent functional disorders and disturbances of the higher nervous activity in the hedgehogs exposed to high temperatures and to promote a better adaptation to heat exposure. The question of vasopressin as a specific antipyretic agent and of its possible clinical use is discussed.     

Comparative pathology of higher nervous activity

In experiments with defensive behaviour, using multiparametric recording of indices, studies have been made on the origin and development of pathological disturbances in the higher nervous activity of insectivores, carnivores and primates during presentation of difficult conditioned reflex problems or extreme stimulation. It was found that elaboration of absolute differentiation retarded conditioned reactions with a delay of 25 s in insectivores is a difficult task which results in pathological changes in the higher nervous activity. In hedgehogs, neurotic changes are immediate, all the investigated indices being affected. In carnivores, especially in primates, the onset of evident pathological changes is preceded by a long preneurotic period, i.e. a stage of self-regulation. In pathological process, more corticalized forms of the nervous activity are initially involved. Common features and differences in the development of pathological changes in the higher nervous activity among mammals are discussed.     

Compensatory and antiamnestic effects of heptapeptide Selank in monkeys

The work presents results of study of role of heptapeptide Selank—an anxiolytic from group of biologically active peptides—in compensation of disturbed psychic and homeostatic functions in monkeys. New data have been obtained which indicate that an intranasal administration of Selank produces long-term changes of the monkey behavior disturbed during neurosis: elimination of fear and aggression and an increase of explorative activity as well as facilitation of handling reactions and communicational relations. It has been established that on the background of the Selank there occurs a long compensation of disturbed psychic functions (processes of memory) and of homeostatic parameters. It has been shown that unlike the earlier studied neurohormones (thyroliberin and ACTH_4?10), the antistress Selank effects do not depend on the type of neurotic disturbances and have long-term compensatory character. Comparison of the data obtained on monkeys with results of similar studies on the more low-organized mammals (rodents) allow suggesting that the new peptide preparation Selank is a promising agent for correction of various psychoemotional disturbances (alarm-and depression-like disorders).     

Conditioned reflex activity and several vegetative reactions in dogs during the recovery period following repeated reanimation]

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.     

Patterns in the ontogenetic development of certain forms of higher nervous activity in rhesus macaques

Studies have been made on ontogenetic development of simple and complex behavioural forms, realization of certain sequence of motor feeding conditioned reflexes, visual differentiation of signals, short-term memory and probability prediction in rhesus monkeys. Evolutionary features of ontogenetic development of some of the forms of the higher nervous activity were revealed. Both similarities and differences were noted in animals from three age groups. In ontogenesis of lower monkeys, the development of the main nervous processes of the higher nervous activity (learning, memory, etc.) takes place gradually depending on the age of a baby and the level of integrative activity of the brain.     

Activity of key redox enzymes in rabbits with different typologic features

It has been found that the activity of LDG, PDG, IDG, SDG, NADN-DG, NADFN-DG, CO, G-6-FDG and 6-FGDG in the cerebral cortex, liver and kidneys of rabbits with a strong type of nervous activity, as a rule, is higher than in the animals with a weak type of the nervous system. Between the animals with different types of the nervous system distinctions are also revealed in the character of regulation of a number of metabolic cycles. It is suggested that typological features of the nervous system are determined by the character of metabolic processes.     

Typological characteristics of conditioned reflex learning in monkeys

Three types of conditioned learning dynamics were singled out in males of the rhesus monkeys by the speed of formation of a positive motor instrumental reflex and differentiation. Type I is characterized by the fastest mastering of separate subprograms and of the whole test program of conditioned behaviour, by optimal functional characteristics in the process of learning and by a high adaptivity in new conditions. The most prolonged formation of the conditioned reflexes occurs in monkeys of the III-d type; 50% of them do not master the whole learning program; monkeys with such type of learning dynamics have no adaptation of previously acquired conditioned stereotype to new environmental conditions. Monkeys of the II-nd type of learning dynamics possess intermediate characteristics. A notion is substantiated of interconnection of higher nervous activity properties with typological characteristics of conditioned learning dynamics in monkeys.     

The effect of cholinergic substances on the mechanisms of visual recognition in monkeys

In monkeys (Macaca mulatta) instrumental reflex was elaborated with differentiation of black-and-white and colour visual stimuli in condition of systemic administration of pharmacological preparations selectively influencing the functional state of cholinergic brain structures. Differentiation of black-and-white and colour stimuli is not disturbed by atropine (0.1 mg/kg) and amizile (up to 1.5 mg/kg) injections; at greater doses frustration of the instrumental reflex takes place. Differentiation of black-and-white and colour stimuli is disturbed at injection of various doses of antidepressant phthoracizine: 5 mg/kg and 7 mg/kg, respectively. These disturbances are restored by the injection of definite doses of galantamine; for correction of colour differentiation a greater dose is required. The obtained data point to differences in neurophysiological and neurochemical processes responsible for black-and-white and colour vision.     

Radiation physiology of higher nervous activity: results and perspectives

Reflex forming and stabilization, the typological peculiarities of the experimental animals' higher nervous activity were discussed. The problems of the central nervous system functional reactions to irradiation in small doses, the chronic irradiation in particular, influence to higher nervous activity of heavy particles irradiation and neurochemical mechanisms of the disturbances in the central nervous system require further experimental investigations.     

The reflection of compensation processes in the structure of the EEG spatial-temporal relationships in patients with disordered brain regulatory mechanisms]

Studies of intercentral relations of electrical activity in the cerebral cortex of the patients with hypophysis tumours under the conditions of chronic (before operation) and acute (after tumour ablation, early post-operative period) influence of the focus on the regulatory brain systems allowed to reveal definite changes of spectral-coherent EEG characteristics, reflecting the functional state of the cerebral adaptive-compensatory apparatus. It has been shown that reciprocal character of changes of various forms of the brain electrical activity and their intercentral relations is one of manifestations of development of the processes of cerebral compensation. At the same time, global fall of the EEG intercentral relations indicating the disintegration of the cerebral functional connections, reflects a loss of CNS compensatory mechanisms. The revealed EEG-characteristics at the present time are applied in Burdenko Institute of Neurosurgery for diagnostic-prognostic estimation of the brain functional state in patients during pre- and post-operative period.     

Functional mediation of compensatory enlargement of the parotid gland

Summary The role of functional activity in mediating compensatory enlargement of the parotid gland after removal of the other major salivary glands was investigated. Increased levels of activity were achieved by feeding rats a bulk diet. Conversely, a liquid diet was used to reduce the functional demands on the parotid. It was found that the liquid diet completely prevented the compensatory response from occurring. Bulk diet, on the other hand, caused an even greater compensatory response than did the standard chow diet. Compensatory enlargement of the parotid, therefore, depends on its functional activity and not on other, e.g., humoral factors dissociated from function. The character of the cellular response in compensatory enlargement was also examined. The chow diet caused compensatory enlargement by an increase in cell size with little, if any, increase in cell number.Supported in part by the Veterans Administration and Grant DE 02110 of the U.S. Public Health Service     

The dynamics of the rats higher nervous activity disturbances after total influence of electrons and gamma-rays in doses 5-100 Gy

The dynamics of using of stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after total influence of high energy electrons and of gamma-rays in doses 5-100 Gy were investigated. The quality structure of higher nervous activity disturbances after the influence of these kinds of ionizing radiation was identical. Therefore the tendency to disturbances aggravating after the electron radiation influence in the periods of the initial depression and of relatively normalization was revealed, especially after the irradiation in dose 50 Gy. The effective compensation of the functional disturbances in the central nervous system at the first 5-10 min after irradiation was after influence of electron radiation in doses about 30 Gy and after the influence of gamma-radiation in doses about 50 Gy. The irradiation of rats in doses 10 Gy and 5 Gy caused qualitative different dynamics of radiation disturbances in rats higher nervous activity. The differences in rats higher nervous activity after influence of electron and of gamma-radiation in these doses did not manifest distinctly.     

Effect of neurosteroid dehydroepiandrosterone on the higher nervous activity of old non-human primates

The results of studies on the biological effects of the prolonged administration of physiological doses of dehydroepiandrosterone (DHEA) on behavior and state of the higher nervous activity (HNA) in old rhesus macaques that had reached the limit of biological age are presented. HNA was investigated using the procedure of motor-alimentary conditioned reflexes, which allows assessing the long-term (conditioned-reflex) memory in animals. The state of short-term (working) memory was evaluated using the test of delayed response performance. DHEA was administered intramuscularly in peach oil at a dose of 1 mg/kg every two days for three months. DHEA at the doses used improved HNA and balanced the excitatory and inhibitory processes in the brain. The motor activity and alimentary motivation were increased. The woolliness lost was restored in old monkeys under the action of DHEA; this effect persisting for a year.     

Effect of enkephalins on the plasticity of pond snail

The effects of introduction of leu- and met-enkephalins (LE and ME) into the perfusion medium on the characteristics of electrical activity, spontaneous firing and habituation of single neurones to repeated intracellular electrical stimulation were studied on isolated CNS of molluscs. The character, speed, and degree of development of endoneuronal habituation changed significantly after application of LE in 67 per cent of the neurones studied and in 25 per cent of neurones after ME application. As a rule the changes of habituation dynamics occurred at constant levels of membrane potential, excitability, and reactivity of the neurone. LE and ME exerted different modulating effects on the initial electrical activity in 60 per cent of neurones. The obtained data on the independence of the effects of enkephalins on different parameters of activity of one and the same neurone give evidence of a mosaic character of excitable neuronal membrane. A suggestion is made about the possible role of the revealed opiate dependence of the endoneuronal functional plasticity in realization of opiate influences at the behavioural level.     

The activity of Krebs cycle enzymes in the visual analyzer of normal rats and under stress]

In the visual analyzer of the intact animals higher activity of NAD-dependent dehydrogenases of tricarbonic acids cycle is observed in the retina and of FAD-dependent dehydrogenases in the occipital brain lobes. The influence of stress by Desiderato method elicits compensatory increase of the succinatedegidrogenase activity. The acute stress elicits a change of regulation of the activity of dehydrogenase of tricarbonic acids cycle, estimated by the reaction to functional load. Animals staying in the darkness after stress promotes restoration of the tricarbonic acids cycle of the enzymes activity up to the normal level.     

The comparative action of relanium and oxytocin on higher nervous activity in lower monkeys]

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.