[ROLE OF CAPSAICIN-SENSITIVE NERVES IN THE REGULATION OF DEHYDROEPIANDROSTERONE SULFATE BLOOD CONTENT UNDER NORMAL AND FRUCTOSE-INDUCED METABOLIC SYNDROME].

The effects of the stimulation of capsaicin-sensitive nerves (capsaicin, 1 mg/kg, s/c) and their eafferentation (capsaicin, 150 mg/kg, s/c) on the blood content of dehydroepiandrosterone sulfate (DHEAS) was investigated in normal rats and rats with fructose-induced metabolic syndrome (12.5% fructose solution, 10 weeks). An increase in blood of tryglyceride, lipid peroxidation, glucose (fasting and after loading glucose, 2 mg/kg, i/p) was considered as symptoms of metabolic syndrome. It was shown that in normal rats drinking tap water the stimulation of capsaicin-sensitive nerves resulted in the increase of DHEAS content while their deafferentation reduced the concentration of this hormone in the blood. The fructose diet caused the decrease in content of DHEAS, triglyceridemia, lipid peroxidation, impaired tolerance glucose. In rats with the metabolic syndrome the stimulation capsaicin-sensitive nerves prevented the fructose-induced decrease of DHEAS content as well as decreased the symptoms of metabolic syndrome. In fructose fed rats the stimulation-induced effects were prevented by the deafferentation of capsaicin-sensitive nerves. It is suggested that capsaicin-sensitive nerves contribute both to the regulation of blood content of DHEAS under normal and fructose-induced metabolic syndrome.

Hypotensive effect of retabolil correcting the concentration of aldosterone during stress exposures.

Male rats were exposed to single or repeated (19 days) cold treatment (4°C) and non-cold stress (60-min shaking on a laboratory shuttle device). Retabolil had a hypotensive effect, which was accompanied by the prevention of a stress-induced increase in the concentration of a hypertensive hormone aldosterone. Under conditions of repeated stress, these effects were realized via µ-opioid receptors. Our results suggest that retabolil can be used as a hypotensive and aldosterone-blocking agent, at least during stress exposure in animals (and probably in humans).

[Farmacological effect of retabolil on aldosterone level and arterial pressure in rats under the action of vibrations].

The experiments were performed on male rats, which were subjected to single and multiply repeated vibrations (low-frequency, horizontal, high-amplitude) analogous to the action of motor transport vibrations. It is established that the administration of retabolil produces a hypotensive effect and blocks the vibration-induced increase in the level of hypertensive hormone aldosterone. Under conditions of the multiply repeated action of vibrations, both effects were realized via micro-opioid receptors. In the case of a single action, these receptors were only involved in a hypotensive effect but not mediated in aldosterone suppression. Both these effects were absent in the control group of animals (not subjected to vibrations). Therefore, retabolil can be used as a hypotensive and aldosterone-blocking drug for vibration-induced hypertension in animals and, probably, in humans.

Parameters of cellular and humoral immunity in experimental hyperthyroidism and its correction.

We demonstrate changes in cellular and humoral immunity in animals with experimental hyperthyroidism induced by chronic administration of potassium iodide (KI) solution. KI increased the weight and cellularity of the thymus and spleen and number of antibody-forming cells to sheep red blood cells and modified the relative content of T cell subpopulations. Phytosorption complex LimfoFit modifying cellular and humoral immunity affected only its individual parameters in hyperthyroid animals.

Effects of dehydroepiandrosterone sulfate on blood pressure and aldosterone level via µ-opioid receptors.

Dehydroepiandrosterone sulfate (30 mg/kg) produced a hypotensive effect by preventing stress-induced surge of hypertensive hormone aldosterone in rats after manifold repeated, but not single stress exposure. Both effects were realized via µ-opioid receptors. Thus, µ-opioid mechanism of blockage of aldosterone surge can underlay the hypotensive effects of dehydroepiandrosterone sulfate at least under conditions of manifold repeated exposures.

Effects of thyroxin and mercazolyl on immunological parameters of blood lymphocytes and lymphoid organs.

Changes in the cellular and humoral immunity parameters were revealed in animals receiving thyroxin and mercazolyl per os for 2 weeks. Specific features of effects of the hormone and its inhibitor on the parameters of immune system were found.

Effect of dehydroepiandrosterone sulfate on aldosterone level during stress exposures: role of µ-opioid receptors.

Dehydroepiandrosterone sulfate (DHEAS, 30 mg/kg) blocks stress-induced elevation of aldosterone concentration in rats subjected to repeated stress. Administration of DHEAS together with opioid receptor antagonist naltrexone in a dose of 0.1 mg/kg, i.e. the dose that selectively blocks µ-opioid receptors, abolished this blocking effect of DHEAS, which suggests that it is mediated by µ-opioid receptors. Under conditions of cold exposure, DHEAS exhibits the aldosterone-blocking effect even after single presentation of the stress factor. However, this effect is realized not via µ-opioid receptors, which attests to differences in the regulatory mechanisms depending on the nature of the external factor.

[The dehydroepiandrosterone sulfate influence on anxiety and depressive behaviour: participation of mu-opioid receptors].

The dehydroepiandrosterone sulfate (DHEAS) influence on anxiety and depressive behaviour was studied in animals after chronic stress exposures. It is shown that DHEAS (30 mg/kg) reduced anxiety in submission (with increased level of stress-induced anxiety resulting from chronic (20-days) defeats in aggressive interactions) of male mice of CBA/Lac strain in the "partition" test and in the plus-maze test, whereas in the control--only in the plus-maze test. DHEAS injection (30 mg/kg) in male Wistar rats decreased depressive behaviour in the Porsolt test in control and multiple (shuttling on the laboratory scrambler for 18 days by 1 hour in day) stressed animals. NaItrexone (0.25 mg/kg in mice and 0.1 mg/kg in rats) blocked anxiolytic and antidepressant-like effects of DHEAS. The findings suggest that these DHEAS effects are mediated by mu-opioid receptors.

[Dehydroepiandrosterone sulfate effect at aldosterone level under cold exposure].

It had been shown that the blockade with dehydroepiandrosterone sulfate (DHEAS) affects enhanced aldosterone level in doses 1, 5 and 30 mg/kg without the dose dependence under multi-repeated cold exposure. These DHEAS effects are realized through micro-opioid receptors. The DHEAS (30 mg/kg) blocking effect was manifested too, but not through micro-opioid receptors under acute cold exposure.

Effect of dehydroepiandrosterone sulfate on the concentrations of thyroxine and triiodothyronine in rats after single or repeated cold exposure.

Repeated cold exposure (4 degrees C) was followed an increase in the concentrations of total thyroxine, free thyroxine, and total triiodothyronine in blood plasma of male rats, while single cold exposure was accompanied by a significant increase only in the concentrations of total triiodothyronine and free thyroxine. After administration of dehydroepiandrosterone sulfate (30 mg/kg), the increase in total thyroxine and total triiodothyronine concentrations became more pronounced after repeated cold exposure, but not after single cold exposure. Dehydroepiandrosterone sulfate did not affect the concentration of free thyroxine after single and repeated cold exposure.

Effects of dehydroepiandrosterone sulfate on the conversion of corticosterone into 11-dehydrocorticosterone in stress: a regulatory scheme.

In male rats, repeated but not single exposures to stress increased the conversion of corticosterone (CS) to 11-dehydrocorticosterone (11-DHCS), particularly on the background of administration of dehydroepiandrosterone sulfate (DHEAS). Naltrexone given 20 min before DHEAS at a dose of 0.1 mg/kg, at which it selectively blocks mu opioid receptors, prevented this effect of DHEAS, which is evidence that it is mediated by mu opioid receptors. This action of DHEAS involved endogenous ACTH and was thus mediated by central regulatory mechanisms. Our results, along with published data, lead to the first proposed scheme for the physiological regulation of the interconversion of CS and 11-DHCS in conditions of repeated stress with the involvement of DHEAS and mu opioid receptors.

[Changes in the thyroid activity and influence of dehydroepiandrosterone-sulfate under the cold and not cold influence].

The dehydroepiandrosterone-sulfate (DHEAS) effect on thyroxine (T4) and triiodothyronine (T3) levels, after the multiple (for 19 days, 1 hr a day) cold (+4 degrees) or stress without cold factor (agitation of rats on the laboratory scrambler) and the possible participation of mu-opioid receptors in this DHEAS effect in male rats. It is shown that DHEAS (30 mg/kg) caused the additional increased T4 and T3 levels indicated the activation of thyroid system. Under multiple stress-factor, the expressed DHEAS-dependent activation of thyroid system, in contrast to the cold-factor, is observed not immediately after action, but only 30 and 120 min after its curtailment, but it is not revealed without DHEAS in the studied time interval. The introduction antagonist of opioid receptor antagonist naltrexone at the dose of 0.1 mg/kg, which it selectively blocks mu-opioid receptors, removes the additional thyroid activation effect of DHEAS, both in cold and in stress factor, indicating the realization in both cases of this DHEAS effect through the mu-opioid receptors, but under the stress-factor but not cold influence the observed phenomenon is set aside time to 30, to 120 min.

[Dehydroepiandrosterone sulfate effect at the conversion of corticosterone to 11-dehydrocorticosterone in stress conditions: the scheme of regulation].

It had been shown that the reaction of conversion of corticosterone (CS) to 11-dehydrocorticosterone (11-DHCS) was increased in chronic intermissions, but not in sharp stress influences in male rats, especially under dehydroepiandrosterone sulfate (DHEAS) employment. The injection of naltrexone 20 min before DHEAS in dose 0.1 mg/kg which selectively blocked the mu-opiate receptors canceled this effect that indicated the participation of in-opiate receptors in such regulation. The DHEAS effect realized through the endogenous ACTH, and such was of the central nature. On the base of ourselves and the literature dates we intraduced the scheme of DHEAS- and mu-opiate-dependent regulation of CS/11-DHCS interchangings.

[The denydroepiandrosterone sulfate thyroid activation through the mu-opioid receptors under cold influences].

Denydroepiandrosterone-sulfate (DHEAS) effects on total thyroxine (tT4), total triiodothyronine (tT3), and free thyroxine (tT4) levels were studied in male rats under single or repeated (for 19 days, 1 hr a day) cold influences, as well as participation of mu-opioid receptor effects in DHEAS (30 mg/kg). It was shown that the increased tT4 and tT3 levels under repeated cold influences were more obvious after DHEAS injections. The opioid antagonist naltrexone in the dose 0.1 mg/kg reversed the DHEAS effect. These data suggest involvement of mu-opioid receptors in that thyroid activation. Under a single cold influence DHEAS did not produce the effects at tT4, or tT3 levels, and the action of mu-opioid receptor blocker in this situation was not manifested. The fT4 levels were obviously increased both under repeated or single cold influences, but the DHEAS and naltrexone actions were absent.

Prolonged decrease in stress reactivity caused by dehydroepiandrosterone sulfate.

In male rats exposed to repeated stress, the decrease in stress reactivity produced by subcutaneous injection of dehydroepiandrosterone sulfate (recorded by the decrease in stress-induced concentrations of corticosterone and adrenocorticotropic hormone in blood plasma) was observed 1-6 days postinjection and involved central regulatory mechanisms.

[Effects of dehydroepiandrosterone sulfate and dizocilpine on memory trace extinction in aggressive and submissive mice].

It was shown that injections of NMDA receptor antagonist dizocilpine and neurosteroid dehydroepiandrosterone sulfate (DHEAS) and sequential injections of these substances had different effects on learning and extinction of passive avoidance in aggressive and submissive mice. In aggressive mice, dizocilpine impaired and DHEAS did not change learning and retention. However, being injected after dizocilpine, DHEAS blocked the defect of memory trace retrieval induced by dizocilpine. In submissive mice, dizocilpine impaired learning and prolonged extinction of the learned habit. Injection of DHEAS prolonged the extinction in a similar way. Under conditions of sequential injections, DHEAS did not change the suppressive effect of dizocilpine on learning and was not effective in prolongation of extinction.

[The influence of dehydroepiandrosterone sulfate on the extinction of passive avoidance in aggressive and submissive mice].

The effects of dehydroepiandrosterone sulfate (DHEAS) on the extinction of passive avoidance was studied on C57Bl/6J mice with aggressive and submissive behavioral stereotypes. Administered in a single dose 30 mg/kg one day or one hour before training, DHEAS selectively blocked the extinction of the conditioned habit in submissive mice, thus favoring its retrieval. The probable mechanism of this phenomenon can be related to a decrease in the level of inhibiting control in the GABAergic system.

[Effect of phenobarbital and thyroxine on hepatocarcinogenesis initiated in mice by nitrosoethylurea and diethylnitrosamine].

13-14-day old mice of ICR and CBA strains were given a single intraperitoneal injection of nitrosoethylurea (80 mg/kg) or diethylnitrosamine (50 mg/kg). 2 weeks later, they were given drinking water containing phenobarbital (1 g/L) or thyroxine (2 mg/L). The control mice were given only tap water. 29.4% of male and 42.1% of female ICR mice who had received nitrosoethylurea died of leukemia within 3-6 months after the carcinogen treatment. There was no case of leukemia in mice treated with diethylnitrosamine. Nitrosoethylurea induced 3-more often lung adenomas than diethylnitrosamine. Phenobarbital and thyroxine did not affect development of either leukemias or lung adenomas. By contrast, phenobarbital significantly elevated the number and size of hepatic lesions, whereas thyroxine markedly decreased them in all the experiments. The total and free thyroxine levels were significantly decreased in the blood of mice given phenobarbital and increased in mice given thyroxine. The data obtained indicate that thyroid hormones suppress tumor development in the mouse liver and that the promotion of hepatic tumoro-genesis by phenobarbital is presumably caused by the elimination of this suppressing effect of the thyroid hormones.

Ratio between the contents of 11-dehydrocorticosterone and corticosterone after acute and repeated stress: effect of dehydroepiandrosterone sulfate.

Acute stress was accompanied by reduction of 11-dehydrocorticosterone to corticosterone in male rats. The reverse reaction predominated during repeated stress and increased after administration of dehydroepiandrosterone sulfate. Treatment with mu-opioid receptor antagonist naltrexone in a dose of 0.1 mg/kg 20 min before administration of dehydroepiandrosterone sulfate abolished this effect.

[Anxiolytic effect of the dehydroepiandrosterone sulfate: mu-opioid mechanism]. / Anksioliticheskii éffect degidroépiandrosteron-sulfata: miu-opiatnyi mekhanizm.

Effects of dehydroepiandrosterone sulfate (DHEAS, 30 mg/kg, i/p, 4 and 28 hours after injection) on CBA/Lac male mice with increased level of anxiety resulting from chronic (20-days) social confrontations in two behavioral anxiety-estimated tests, were studied. The anxiolytic effect of DHEAS was discovered within 4 hours after injection in the "partition test" of social interactions and within 28 hours in "plus-maze test". Naltrexone (0.25 mg/kg, for 20 min before DHEAS injection) blocked this effect.