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Nuruddinov Eshon Nuritdinovich, doctor of biological sciences, professor, Department of Physical Education, Samarkand State University Rakhmatova Nigora Boturovna, assistant of the Department "Human and Animal Physiology and Biochemistry" of Samarkand State University E-mail: baxritdin-bazarov@rambler.ru
THE ROLE OF NEUROPEPTIDE DERMORPHINE IN THE PROCESSES OF HIGHER NERVOUS ACTIVITY IN FALSE HEAT (HEMIECHINUS AURITUS)
Abstract: The role of neutropened dermorphine in the treatment of upper respiratory tract (Hemiechinus Auri-tus). In the article, the authors point out that the pelvic dystrophy of the upper nervous activity may have a negative effect on dermorphine injection, in addition to the normal analgesic effect.
Keywords: dermorfin, opioids, phelomedusa, refleks, thermoregulation, hibernation, organism, neyropeptids, mammals.
Dermorphin (DM) is one of the most active natural opioids, isolated from the skin of frog Phylomedusain 1980. However, its impact on the behavioral activity of mammals is least studiedtill date. In earlier work [1, 3-5] it has been reported that the introduction of DM to rats is accompanied by a pronounced analgesic effect and change in motor activity. It is interesting to study the effect of DM on conditioned-reflex activity of insectivores - hedgehogs, the lowest organized mammals belonging to the group of hibernating animals.
Methods. The work was performed on 9-year-old hedgehogs on a model of obtain food. In hedgehogs, positive conditioned reflexes, various types of internal inhibition were studied: extinctive, differentiating, delayed in normal conditions, with pathological disorders of higher nervous activity (HNA) and changes in these forms of nervous activity after the introduction of DM. Neurotic changes in
hedgehogs were caused by the development of fine differentiation or delayed inhibition with a lag time of more than 30 s. Dermorfin (Serva) with saline was injected subcutane-ously at a rate of 0.1 mg/kg immediately, prior to the experiment. At the end of the experiments, the experimental data wasobtained and processed employing accepted statistical methods using student's criterion.
Figure 1. Changes in the analgesic threshold of the motor reaction in hedgehogs after administration of dermorphin. The ordinate is the irritating current (V) in volts; abscissa - time in minutes and days; the arrow is the moment of introduction of the demorphine. Asterisks indicate confidence levels: * - p < 0.05; ** - p < 0.01; *** - p < 0.001
THE ROLE OF NEUROPEPTIDE DERMORPHINE IN THE PROCESSES OF HIGHER NERVOUS ACTIVITY IN FALSE HEAT (HEMIECHINUS AURITUS)
Results: It has been established that the development of fine or absolute differentiation, as well as delayed conditional reactions, wasa difficult conditional-reflex task for hedgehogs, leading to disruptions of HNA. The development of pathological disorders of HNA is accompanied bychanges in the temporal parameters of the conditioned reaction of food obtain (1st stage), the appearance of vegetative disturbances, an increase in the number of intersignal reactions, the occurrence of cardiac reactions (2nd stage), a fall in food unconditional reactions, the emergence of trophic and somatic disorders (3rd stage).
The introduction of dermorphin to neurotic hedgehogs caused pronounced behavioral changes, some can be conditionally divided into 3 periods.
The first period is the period of maximum changes - from 5 minutes to 4 hours after administration. It was characterized by pronounced vegetative, somatic and behavioral disorders, consisting of the initial appearance of such sympathetic effects as: tachyrhythmia, tachypne (P < 0.05), hyperemia and injection of auricular vessels. After 30 min of introduction, the sympathetic effects were replaced by parasympathetic, such as: salivation, significant decrease in respiration (on 54 ± 2.5%), decrease in heart rate (on average by 37 ± ± 0.27%). The animals plunged into a sleepy state. Tactile sensitivity decreased: there were no reactions to touching the animal with the hands of the experimenter or the hot plate (hot plat test). During this period, the body temperature dropped gradually from 37-36 °C to 20-17 °C by the first hour after injection. Food excitability was absent.
On the background of the introduction of DM in hedgehogs, a pronounced analgesic effect is revealed. The threshold of nociceptive irritation of the forepaw with its subsequent withdrawal reaction (paw flick) increased 5-7 times compared with the preinjection period and remained at this level for 4 hours after administration (Fig. 1).
The second period was characterized by a partial recovery of conditioned reflex activity, unconditional food reactions, the emergence and intensification of neurotic disorders. The increase in neurotic disorders was particularly pronounced from the 6th to the 10th day after the introduction of DM. It consisted of a significant shortening of latent period of time the hedgehog emerged from the starting compartment to (1-2) ± 0.3 s with neurosis of an excitable type or its lengthening to (12-15) ± 0.8 s (at a rate of 4.2 ± -0.5 s) with neurosis on the brake type. The time of return of hedgehogs to the starting compartment was significantly lengthened up to 35-60 s (at a rate of 15-18 s).
The appearance of paradoxical and ultra paradoxical relations was observed. In animals, motor anxiety was detected, the number of intersignal actions increased to 25-30 in one
experimental day (at a rate of 4-6). Endless carding reactions were detected.
From the 6th to the 10th day, food excitability was reduced, despite prolonged food deprivation. So, in response to a conditional signal, the hedgehog ran out from the starting compartment, approached the reinforced feeder, performed a food-producing reaction, but did not eat food, or, going up to the reinforced feeder, made intense carding reaction. One of the characteristic features of the effect of dermorphin during this period is a significant violation of all the studied types of internal inhibition. Differentiation inhibition, as a rule, was absent. Delayed conditioned reactions were disinhibited. This could be most clearly illustrated by the example of extinguishing inhibition.
It has been found that in hedgehogs after the introduction of DM, there is a significant difficulty in the formation of extinctive inhibition and a change in its dynamics. Unlike intact animals, the use of 20 non-reinforcements did not lead to a lengthening of the temporal parameters of the conditional food-producing reaction: the exit time from the starting compartment continued to be short (1-2 s). There was only a gradual shortening of the time for the hedgehog to return to the starting compartment, which shortened to 6-13 s instead of 40-50 s by the 14th to 15th time instead of 40-50 s, which occurred when the first back-up was presented. The extinction of conditional food-receiving reactions against the background of the introduction of DM came after 30 refusals at a rate of 15-17 reflexes (Fig. 2).
An interesting feature of the changes in HNA in the second period is the strengthening of orientational research activities. So, hedgehogs "examined" the experimental chamber, took "vertical racks". Similar phenomena did not occur in hedgehogs before the administration of the drug. It should be noted that despite significant conditioned reflex changes, the analgesic effect during this period was absent. The body temperature of the animals was within the normal range.
The third period from the 10th to the 20th day after the introduction of dermorphine was characterized by normalization of the conditioned reflex activity, some general calming of the animal. Neurotic reactions did not completely disappear, but they did not manifest themselves to such a bright degree as was observed in the second period. Food excitability was fully restored. Thermoregulation and vegetative (heart rate and respiratory movements) indicators were at the level of intact animals.
The antinociceptive effect was completely absent. However, the development of extinctive inhibition had a slightly different dynamic than that of intact animals. Thus, it was found that the development of extinctive inhibition for hedgehogs is a difficult task. With the increase in the
number of necks, the appearance of neurotic reactions, manage movements, intersignal reactions and motor anxiety was observed. The introduction of physiological solution in the control experiments did not change neither the conditioned reflex activity, nor the thermoregulation and vegetative indices. Thus, the data presented indicate that at the insectivorous level, the introduction of dermorphine leads to significant behavioral disorders, accompanied by changes in the vegetative-vascular and thermoregulatory systems.
A comparison of the data obtained with the literature, performed in the same aspect in rodents [3, 7-11], suggest that the effect of DM is more pronounced and significant in insectivores. It can be assumed that this opioid peptide has a species-specific effect: its effect is more pronounced in hibernating animals. This assumption is supported by the results of our studies on lizards [2, 12-15]. These data are generally consistent with the hypothesis of Lipman [5, 6-8], according to which,, the action of dermorphin can be considered as a primitive mechanism of protein synthesis previously used in evolution.
Thus, the data presented indicate that the introduction of an opioid peptide - DM, according to a typical analgesic effect, has a significant impact on the functional state of insectivores. With the introduction of DM, significant changes in innate and acquired forms of nervous activity were found. The internal braking processes are more affected. Is this effect on GNI processes secondary, due to the effect of DM on the hypothalamic, in particular, thermoregulatory centers of the anterior hypothalamus, as evidenced by a significant drop in body temperature, andas a consequence, the animal's falling into a shearing state, * or such changes are the result of the binding of DM to opiate receptors of structures the limbic brain, or finally, this change in the functional state is a species-specific reaction, characteristic only for hibernating animals, it is a question of the future special comparative physiology based surveys, using both electrophysiological and immunohistochemical methods. A partial answer to it will be given in our next messages with the use of DM conjugate in insectivorous and various species (winter-sleeping and non-sleeping) rodents.
References
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