9th multidisciplinary international

Conference of Biological Psychiatry

«Stress and Behavior»

Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005

Editor: Allan V. Kalueff, PhD

CONFERENCE ABSTRACTS

4. EXPERIMENTAL MODELS: M.A. DERYAGINA MEMORIAL SYMPOSIUM

EVOLUTIONARY PECULIARITIES OF NEUROHORMONAL STRESS COMPENSATIONS IN THE ASCENDING ROW OF MAMMALS

T.N. Sollertinskaja, M.V. Shorohov

Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg, Russia

The search for adequate methods to increase the organism resistance to different stress influences, and the post-stress compensatory mechanisms, is one of the key problems in neurophysiology and medicine. In the last decades, the problem has become especially key because of the social-economic problems, growing technogenic and natural catastrophes, wars, terrorism and their consequences. The important role of the emotional stress mechanisms belongs to neuropeptides especially opioids (P-endorphin). Ealier it was established that the mammals B-endorphin conjugate immunization was accomponied by a long term compensation of neurotic disturbances (Karamjan, Sollertinskaja, 1987). The Higher Nervous Functions are the first to suffer from different stresses (Alekseeva, Gusev, 2000). At present, neurohormones of hypothalamus (or their fragments) such as vasopressin (VP), thyroliberin (TRH) and ACTH4-10 (Pro-Gly-Pro — Semax) are used in our clinics and abroad (Ashmarin 2000, Gusev, 2000). It has been shown that the role of VP in the compensation of brain pathogenesis increases with evolution. The comparative-physiological studies of the TRH and ACTH4-10 role in the brain functional compensation at different stresses are almost lacking. The present work assesses comparative roles of hypothalamic hormones TRH and ACTH4-10 and their stress-correcting properties in ascending row of mammals: insectivores, rodents and primates. The experiments used food model and multiparameter (EEG, vegetative, motor) registration of behavior. The first series was performed on freely moving animals, the second used monkies placed into primatological chair. Besides the positive conditional reflexes some kinds of internal inhibition such as extinction, differentiation have been investigated. The following types of memory were studied: conditional (the delayed conditioned reflexes — DCR), image, short-term and long term memory. The drugs: TRH, ACTH4-10 «Serva» were induced intranasally 10 min prior to the experiments at 3—5 mkg/kg and 0.01—0.1 mkg/kg, respectively. Neurotic disturbances were provoked by overloading analytico-synthetic brain activity or by extremal conditions. In hedgehogs with neuroses, TRH and ACTH affects are uniform, and mostly affect inherent forms of behavior, increasing motor, inter-signal, exploratory activity. The food positive conditional reflexes are restored. The extinction is quickly formed. DCR was seen only for a short delay up to 15s. The absence of definite pattern of conditional response as well as the presence of vegetative conditional reactions during the sound phase and the delayed one are both characteristic of memory processes in hedgehogs. The respiratory conditional reactions (CR) are more robust (up to 80%). The level of cardiac CR is rather low (30%) and its pattern unclear. TRH and ACTH influences on hedgehogs memory had different nature: small doses of TRH (3mkg/kg) exert inhibitory effects on motor and visceral memory components, whereas ACTH increased DCR for a short-term memory (1 day). In contrast to hedgehogs, DCR formation in rabbits and rats was possible with some longer delay (25s), showing a tendency to intensify memory. The TRH influence on various vegetative parametrs are different. The level of the respiratory CR of delay phase is increased. The pattern of respiratory of rate

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 905-906

Psyhopharmacology & biological narcology

ISSN 1606-8181

diminished response in delay phase becomes dominant. But the cardiac CR were present in the sound as well as the delayed phases, and had no clear-cut pattern. ACTH administration leads to a short-term 3-day DCR restoration. It has been established that two types of monkey's neurosis may be distinguished: excitatory and inhibitory (ET, IT accordingly). The neurosis induces the marked disturbancies of heart activity such as tachicardia, extrasistolia. The diffuse changes including reduced alpha-rythm, appearance of teta and delta intervals, were observed in EEG. In neurotic monkies, TRH and ACTH exerted different effects on disturbed brain functions. The compensatory effect of TRH are more expressed at IT. On the TRH background, EEG was similar to the awake state. The positive CR are restored especially on EEG and respiratory parameters. The image memory is intencifited for a long time (5—7 days). The influence of TRH upon DCR is of facilitatory character. In contrast to TRH, ACTH compensatory effects are more expressed at ET. After administration of ACTH, DCR were restored and increased, the time delay increased 2-3-fold, and the baseline EEG was normalizied. Desynchronization was more pronounced at delay phase. The respiratory rate becomes rarer. After ACTH at ultra small doses, some sedative effects appeared. These effects are recorded for a long time (10—14 days). Thus, the data obtained have shown that the compensatory role of hypothalamus neurohormones at the disturbances Higher Nervous Functions is increased in the process of evolution. At the lower level of mammalian evolution the TRH and ACTH compensatory influence is more expressed in inherent forms of behavior. These effects are wholly uniform on the simple forms of Higher Nervous Activity. The differentiation of TRH and ACTH influence on memory is expressed as a tendency. The effects of TRH and ACTH on brain disturbances in primates have specific features. The compensatory effects of TRH are more important for inhibitory types of neurosis; while the ACTH is critical the excitatory neurosis. Collectively, these data may serve as a neurophysiological backround for differentiated clinical application of such neurohormones.

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 905-906

Psyhopharmacology & biological narcology

ISSN 1606-8181