[Respiratory responses to microinjections of gastrin-releasing peptide into the solitary tract nucleus].

In acute experiments on urethane-anesthetized rats, the respiratory effects ofmicroinjections of 10(-5), 10(-8) and 10(-10) M gastrin-releasing peptide (GRP) into the solitary tract nucleus were investigated. It was found that microinjections of the neuropeptide induced an increase in tidal volume, amplitude of diaphragm and external intercostal muscles firing activity and in expiratory duration. The most obvious respiratory responses observed when 10(-8) M GRP was used, while 10(-10) M GRP appeared to be sub-threshold and didn't alter the breathing pattern and activity of inspiratory muscles. In some experiments, where the blood pressure and the heart rate was monitored alone with breathing pattern, these parameters did not change after GRP microinjections into the solitary tract nucleus. The obtained data together with particularities of the distribution of GRP receptors in the brainstem suggest the possibility of GRP involvement into the respiratory control mechanisms at the level of solitary tract nucleus.

[The effect of insulin on circadian rhythm of voluntary locomotor activity in rats].

Effects of single intranasal administration of 0.2 ng insulin at different moments of the projected daily cycle (ZT = 1, ZT = 7, ZT = 13 and ZT = 19) on the circadian rhythms of voluntary locomotor activity (wheel-running) were studied in Wistar male rats. Insulin administered at ZT-7 or ZT-13 induced a statistically significant phase advance by 4.4 and 5.5 hours, respectively. The administration of insulin at ZT-13 additionally induced a reduction of the period of the circadian rhythm of voluntary locomotor activity. Intranasal administration of insulin at other moments of the projected daily cycle (ZT = 1 or ZT = 19) did not induce any statistically significant change in phase or period duration of the circadian rhythms. Insulin did not cause changes in total daily activity irrespective of administration time. The results of the study suggest the role of endogenous insulin as entrainment factor for circadian oscillator in absence of the main physiological zeitgeber--cyclic afferent input from retina photoreceptors.

[Local GABA-ergic modulation of serotonergic neuron activity in the nucleus raphe magnus].

In voltage-clamp experimental on slices of the rat brainstem the effects of 5-HT and GABA on serotonergic neurons of nucleus raphe magnus were investigated. Local applications of 5-HT induced an increase in IPCSs frequency and amplitude in 45% of serotonergic cells. The effect suppressed by the blocker of fast sodium channels tetradotoxin. Antagonist of GABA receptor gabazine blocked IPSCs in neurons both sensitive and non-sensitive to 5-HT action. Applications of GABA induced a membrane current (I(GABA)), which was completely blocked by gabazine. The data suggest self-control of the activity of serotonergic neurons in nucleus raphe magnus by negative feedback loop via local GABAergic interneurons.

[Mechanisms of the respiratory activity of leptin at the level of the solitary tract nucleus].

In acute experiments on anaesthetised rats we investigated the effects of 10(-4) M leptin microinjected into the solitary tract nucleus on inspiratory-terminating Breuer-Hering reflex and ventilatory responses to hypercapnea. We found that the local administration of leptin into the area inhibited the inspiratory-terminating Breuer-Hering reflex. In contrast, ventilatory responses to hypercapnea were accentuated suggesting a modulatory effect of leptin on central chemoreceptors. The discovered physiological mechanisms are likely to play a key role for stimulating respiratory effects of leptin at the level of the solitary tract nucleus.

[Respiratory responses to microinjections of leptin into the solitary tract nucleus].

Regulatory polypeptide leptin, apart from its well-known hypothalamic effects, stimulates ventilation. The present study on anaesthetised rats was undertaken to elucidate the respiratory effects of 10(-10)-10(-4) M leptin microinjected into the solitary tract nucleus, containing a high concentration of leptin receptors. Injections of 10(-8)-10(-4) M leptin induced dose-dependent increase in ventilation, tidal volume and electric activity of inspiratory muscles; 10(-6) M leptin additionally induced a short-term increase in respiratory frequency and a shortening of both inspiratory and expiratory duration. The respiratory responses to leptin is also characterised by appearance of sighs: deep and prolonged inspirations associated with an augmented burst in the activity of the inspiratory muscles and prolonged post-sigh inter-burst interval. The results taken together with evidence of high concentration of specific leptin ObRb-receptor in the solitary tract nucleus suggest involvement of endogenous leptin in the control of breathing via dorsal structures of the respiratory center.

[Respiratory effects of bombesin at the level of pre-Botzinger complex in rats].

Respiratory effects of 0.1 pM - .1 mM bombesin microinjected to the pre-Botzinger complex were studied in anaesthetised rats. Bombesin induced an increase in minute ventilation, respiratory frequency, a decrease in expiratory duration and shortening of inter-burst intervals on the EMG of diaphragm and external intercostal muscles. The responses to bombesin characterised by short latency, quick development (with the maximum in 3-minutes after microinjection) and found to be reversible. The effects of bombesin on membrane potential, input resistance and pattern of spontaneous activity ofpre-Botzinger neurons were investigated in brainstem slices. 1 nM bombesin introduced into the perfusion solution in most cases (68%) induced membrane depolarisation, an increase in input resistance and in spike activity of spontaneously active cells. The data obtained suggest that the respiratory effects ofbombesin at the level ofpre-Botzinger complex are caused by its action on the membrane of neurons.

[Effect of leu-enkephalin on potassium currents in neurons of the respiratory center of rats in vitro].

Action of opioid peptide: leu-enkephalin (10 nM - 1 microM), on K+A-current and inward rectifier in neurons of two divisions of the respiratory center: ventrolateral area of the solitary tract nucleus and the pre-Botzinger complex, was investigated in brainstem slices of Wistar rats by whole-cell voltage-clamp recordings. A-current and inward rectifier were found in all the neurons under study. A-current did not change after the application of leu-enkephalin to the bath solution while the amplitude of inward rectifier did reversibly increase. The data obtained suggest that the inhibitory effect of leu-enkephalin on neurons of the respiratory center, at least in part, can be based on its ability to modulate inward rectifier.

[The effect of leu-enkephalin on membrane potential and activity of the rat respiratory center neurons in vitro].

In frontal brainstem slices of Wistar rats, the whole-cell patch-clamp recordings showed the effect of opioid peptide leu-enkephalin (10 nM-1 microM) on membrane potential and spontaneous activity pattern of neurons in two divisions of the respiratory center, ventro-lateral area of the solitary tract nucleus, and the pre-Bötzinger complex. Leu-enkephalin induced a membrane hyperpolarization of the respiratory centre neurons and reduction of the spike activity level in spontaneously active units. After administration of leu-enkephalin, a decrease in frequency of bursts was found in bursting cells of the pro-Bötzinger complex; in two cases, there was a transition of bursting activity to tonic one. The data suggest that the mechanism of the central respiratory activity of leu-enkephalin is based on its direct action at the level of membrane of the respiratory centre neurons.

[Features and mechanisms of realization the respiratory influences of the extrapyramydal system structures]. / Osobennosti i mechanizmy realizatsii respiratornykh vliianii struktur ékstrapiramidnoi sistemy.

In the publication the modern condition of the problem of suprabulbar regulation of breathing is analysed. The review on structure, neurochemistry and anatomic connections of the red nucleus and substantia nigra with the medullary respiratory center is submitted. The data on the respiratory effects of GABA and apomorphine microinjected into the red nucleus and substantia nigra as well as effects of their electrostimulation after the blockade of GABA and dopamine receptors in the respiratory center are discussed. The conceptual scheme of the mechanisms of realization the respiratory influences of the extrapyramydal system is offered.

[Neuropeptide thyroliberin in ultra low doses--anticonvulsant defense of the brain]. / Neiropeptid tiroliberin--protivosudorozhnaia zashchita mozga v sverkhmalykh dozakh.

Thyroliberin (TRH) promoting endogeneous antidepressive effect is the most general regulator of the central mechanisms and visceral functions (especially respiration). Our group pioneered in applying the anticonvulsant action of TRH after local intranasal application). This application of TRH in ultra-low doses contrast the method of systemic TRH administration in the large doses). In our experiments intranasal application of 10(-8), 10(-10) and 10(-12) mol/l TRH significantly inhibited the severe epileptic motor fits in rats induced by PTZ. EEG also confirms beneficent effect of TRH (TRH suppressed SWD in cortex, amygdala and hippocamp). In the experiment that follows compared effects of TRH (pyroGlu-His-Pro-NH2) and its metabolite dipeptide His-Pro (10(-10), 10(-8) mol/l). The experiments make more precise that only TRH but not His-Pro posses the anticonvulsant properties. There is a good believe that medical potentialities of TRH have not been exhausted and its new possibilities of its usage will be revealed in epileptology.

[Thyroliberin blocks potassium A-current in neurons of the respiratory center of adult rats in vitro]. / Tiroliberin blokiruet kalievyi A-tok v neironakh dykhatel'nogo tsentra vzroslykh krys in vitro.

TRH is a well-known respiratory active neuropeptide. To study neuronal mechanisms of its activity, we have tested the effects of TRH on the potassium A-current in neurons of the ventrolateral solitary tract nucleus and pre-Botzinger complex in voltage-clamp experiments on adult rat brain slices. A-current was present in the neurons and it was partially and reversibly blocked by administration of THR (10(-8) M) to the bath solution. The significant decrease in amplitude of A-current was accompanied by the increase in inactivation constant (t). The effect of TRH on A-current amplitude was simulated by 5 mM 4-aminopyridine. The results presented here indicate that the stimulatory effects of TRH on neurons of the respiratory centre can be at least partially explained by its ability to block the potassium A-current.

[Comparative characteristic of respiratory pattern responses to kainic acid microinjections in different parts of the nucleus ambiguous]. / Sravnitel'naia kharakteristika reaktsii patterna dykhaniia na mikroin''ektsii kainovoi kisloty v razlichnye otdely dvoinogo iadra.

In rats, local chemical isolation of neurones by the kainic acid helped to investigate into comparative role of different parts of the n. ambiguus in respiratory control mechanisms. We disclosed specific peculiarities of responses of rhythm and respiratory pattern to chemical isolation of different parts of the n. ambiguus. In particular, it was found that consecutive isolation of the left and right rostral parts of the n. ambiguus caused a significant decrease of the respiration rate and respiratory volume and also resulted in irreversible cessation of respiration in 83% of experiments. Isolation of symmetric medial parts of the n. ambiguus resulted in bradypnoe and a decrease of pulmonary ventilation; maximal respiratory effect was recorded after kainic acid injection in the symmetric part only, thus the irreversible cessation of respiration was recorded in 50% of experiments. After isolation of symmetric caudal parts of the n. ambiguus we observed an insignificant decrease of the respiration rate without significant changes of the respiratory volume, and number of the respiration cessation was minimal: 33%.

[Effect of thyroliberin on membrane potential and pattern of spontaneous activity of neurons of the respiratory center in rats in vitro]. / Vliianie tiroliberina na membrannyi potentsial i pattern spontannoi aktivnosti neironov dykhatel'nogo tsentra in vitro u krys.

On frontal brainstem slices of rat by means of whole-clamp recordings, we investigated effects of TRH (10(-8) [symbol: see text]) on membrane potential and firing pattern of the neurones in ventrolateral area of the solitary tract nucleus and pre-Botzinger complex. TRH induced a membrane depolarisation and an increase in spontaneous activity of the respiratory centre neurones. After TRH administration, a shortening of time intervals between the beginning of bursts was found in bursting neurones of the pre-Botzinger complex. In some silent neurones, TRH elicited appearance of firing activity, so the silent neurones of the solitary tract nucleus were transformed into tonic while the silent pre-Botzinger complex neurones were transformed into bursting ones. Thus, there is a direct regulatory effect of TRH on the respiratory centre neurones at the level of their membrane.

[Pre-Bötzinger complex participates in respiratory effects of thyroliberin]. / Kompleks pre-Betzingera uchastvuet v realizatsii respiratornykh éffektov tiroliberina.

Responses of the TRH microinjections into the pre-Bötzinger complex of adult anesthetised rats involved a dose-dependent increase in respiratory rate as well as shortening of inspiratory and expiratory duration. The tidal volume and inspiratory muscles' activity decreased following high concentrations of the TRH. The heart rate did not change. The findings suggest that the pre-Bötzinger complex is at least partly responsible for the TRH tachypnoic effect.

[The effect of tachykinins microinjections into the solitary tract nucleus on respiration and blood circulation in rats]. / Vliianie mikroin''ektsií takhikininov v oblast' iadra solitarnogo trakta na dykhanie i krovoobrashchenie u krys.

Administration of substance P and kassinin into the solitary tract nucleus of anesthetized rats induced a dose-dependent increase in ventilation, tidal volume, inspiratory muscle activity, and a decrease in the mean blood pressure and heart rate. Microinjections of peptides caused a decrease in ventilatory response to hypoxia and an inhibition of the Breuer-Hering reflex. The data obtained suggest involvement of tachykinins in the respiratory and circulatory control via the solitary tract nucleus.

[Respiratory and hemodynamic responses to microinjections of opioids into the solitary tract nucleus]. / Respiratornye i gemodinamicheskie reaktsii u krys na mikroin''ektsii opioidov v iadro solitarnogo trakta.

Microinjections of morphin and leu-enkephaline into the solitary tract nucleus of anaesthetised rats induced a dose-dependent decrease in tidal volume and in external intercostal muscle activity. In addition, leu-enkephaline and -endorphine decreased the respiration frequency. The respiratory effects were accompanied by a decrease in the mean blood pressure and heart rate. Naloxone administration exerted an opposite effect. The data obtained suggests an involvement of opioid peptides in respiratory and circulatory control via the solitary tract nucleus.

[The effect of thyroliberin microinjections into the area of the nucleus tractus solitarii on respiratory and circulatory indices]. / Vliianie mikroin''ektsii tiroliberina v oblast' iadra solitarnogo trakta na pokazateli dykhaniia i krovoobrashcheniia.

The TRH administration induced an increase in ventilation, essential changes in breathing pattern and activity of the inspiratory muscles in anesthetised rats. The doses 10(-12)-10(-8) M TRH decreased the heart rate, whereas 10(-10) M TRH increased the blood pressure. The data obtained suggest an important role of the nucleus tractus solitarii in realization of the TRH respiratory and circulatory effects. The data obtained corroborate the hypothesis of the participation of endogenous TRH in the respiratory and circulatory control.

[The respiratory reactions to thyroliberin action on the ventral surface of the medulla oblongata]. / Dykhatel'nye reaktsii pri vozdeistvii tiroliberina na ventral'nuiu poverkhnost' prodolgovatogo mozga.

Applications of the TRH to the brain stem ventral surface of anesthetized rats increased the lung ventilation and essential changes in the breathing pattern. At the same time, electrical activity of inspiratory neurons was enhanced and that of expiratory neurons reduced (the ambiguous nucleus area). The data obtained suggest a major role of ventrolateral medulla in realization of the TRH respiratory effects.