[Vascular reactivity and receptor expression of endogenous vasoconstrictor in rats with alcoholic cardiomyopathy and insulation stress].

On the model of alcohol cardiomyopathy studied the effect of chronic ethanol consumption and the insulation stress on the reactivity of isolated rat aorta and the expression of the endogenous vasoconstrictor receptors in the aorta. Pushing alcoholization outbred rats was carried out for 24-28 weeks, using as the sole source of liquid 10% ethanol solution. In assessing the results of the study took into account the age of the animals. It is found that the reactivity of isolated aortic rings dissected from the body of old (40-45 weeks) nonstressed rats in response to endothelin-1 (ET1), noradrenaline (NA), arginine vasopressin (AVP) or angiotensin II (ATII) is not different from such reactivity for young animals. However, with the increase in life expectancy increases the sensitivity of vessels to vasoconstrictor action of serotonin (5HT). Prolonged stress insulation and the consumption of high doses of ethanol the stress lead to increased ET1- and NA-induced contraction of the aortic rings and a significant decrease in contractile response of the aorta to the impact ATII and AVP. Stress and alco- hol in combination with stress causing reduction mRNA ETA-R, AT1A-R. and V1A-R and increased mRNA α1-AR in rat aorta. It is found that in the vessels of stressed and alcoholized animals reduced level of expression of cytosolic glucocorticoid receptors (GR), which is a transcription factor for genes ETA-R, AT1A-R V1A-R. It is propoused that the development of vascular hyporesponsiveness of stressed and alcoholized rats to action ATII and AVP is the result of reducing the expression of their receptors on the GR-dependent mechanism. It is shown that under the influence of ethanol vessels become hyporeactivity selectively with respect to the action of 5HT. The mechanism of this process is unclear. Importantly, the changes in the contractile properties vessels recovered from the rat at 1 month after the abolition of the reception of ethanol (step abstinence) were similar to changes found at the alcohohzed animals. Thus, the importance of breaking the neuroendocrine regulation of vascular tone during long-term consumption of ethanol has a stressor components. Furthermore, in this experimental model we not received data in favor ethanol direct impact on the development of hypertension.

[Pharmacological analysis of the participation of the catecholaminergic system in the development of the abstinence syndrome in rats]. / Farmakologicheskii analiz uchastiia katekholaminergicheskoi sistemy v razitii abstinentnogo sindroma u krys.

The behavioural activity of rats in "the open field" was studied. It was revealed that rats alcoholized for 8 months do not practically differ in their behavioural indicators from the intact ones. After the discontinuation of alcohol marked disturbances appear in their behaviour, that are arrested by apomorphine (0,1 mg/kg). In intact animals dopamine (50 mkg into the brain ventricles) induces behavioural disorders similar to those in rats during abstinence. Noradrenaline does not induce similar disorders. A conclusion is made on the dopaminergic nature of disorders in the behaviour of rats in the state of alcohol abstinence.

[Effect of the destruction of the brain serotoninergic system on the alcohol consumption by rats in the early periods of experimental alcoholism]. / Vliianie destruktsii serotoninergicheskoi sistemy mozga na potreblenie alkogolia krysami na rannikh srokakh éksperimental'nogo alkogolizma.

Albino noninbred rats were divided into groups, according to the duration of alcoholic anesthesia (4.5 g/kg i.p.), of predisposed (195.6 min) and non-predisposed (69.1 min) to voluntary intake of alcohol. Another group included animals screened for 21 days according to the level of intake of 15% ethanol under the conditions of free choice between alcohol and water (6.15 and 2.62 g/kg pure ethanol per day, respectively). The animals were subjected to electro-coagulation of the dorsal or magnus raphe nucleus or were injected with 5,6-dihydroxytryptamine--DNT (75 micrograms/microliters) into the ventricles of the brain. It was established that in rats non-predisposed to alcohol intake, the destruction of the raphe nuclei, of the dorsal in particular, or injection of DOT to animals with a weak alcoholic motivation produces a dramatic increase in alcohol intake. In alcohol intake predisposed rats and in animals with a high level of alcohol use, analogous exposures do not bring about any significant differences in alcohol intake. The data obtained indicate that the reduced serotonin content in the brain is associated with an increase in the level of alcoholic motivation.

[Catecholamine content of the rat brain at different stages of experimental alcoholism]. / Soderzhanie katekholaminov v mozge krys na raznykh stadiiakh éksperimental'nogo alkogolizma.

Changes in the noradrenaline (NA) content in the hypothalamus, dopamine (DA) and homovanillic acid (HVA) in the striatum were determined in rats after chronic alcohol administration. A single injection of alcohol (2.5 g/kg i.p.) provoked a 30% decrease in NA only in rats predisposed to ethanol intake. Voluntary intake of 15% ethanol for 10 days made the NA content return to normal, the 4-month use of ethanol did not change whereas the 8-month use reduced the NA content by 17%, DA by 31% and raised the content of HVA by 25%. Twenty-four hours after alcohol abstinence the HVA content dropped by 13%. It is concluded that the noradrenergic system is involved in the formation and development of alcohol motivation and that the dopaminergic system participates in the development of the physical dependence and abstinence.

[Tyrosine hydroxylase activity in the brains of rats with different levels of initial alcoholic motivation]. / Tirozingidroksilaznaia aktivnost' v mozge krys s razlichnymi urovniami iznachal'noi alkogol'noi motivatsii.

Activity and KM of hypothalamic tyrosine hydroxylase (TH) were studied in rats preliminarily tested for predisposition to high ethanol consumption. It was shown that as regards cofactor of DMPH4 enzymatic reaction, KM of hypothalamic TH of animals with an initially high alcoholic motivation is lower than that from the brain of animals rejecting alcohol, being 0.34 +/- 0.3 mM and 0.46+/- 0.10 mM, respectively. A conclusion is made that the catecholaminergic system is involved into the realization of the rewarding effects of ethanol.