[Is ethanol a stressogenic factor for rats with a developed alcohol motivation?]. / Iavliaetsia li étanol stressogennym faktorom dlia krys so sformirovannoi alkogol'noi morivatsiei?

The male outbred rats, placed in common cages, demonstrated dose- and time-dependent increase of blood plasma ACTH level after handling and acute ethanol administration (1 and 4 g/kg). The pituitary response of isolated rats under condition of free choice between water and 15% ethanol solution was more pronounced after handling. Ethanol (4 g/kg) did not increase plasma blood level ACTH in isolated alcohol motivated rats. It also prevented blood plasma ACTH rise under condition of handling. The dual role of acute ethanol as a stressogenic and antistressogenic factor in naive and alcoholic rats is discussed.

[Positive modulation of diazepam activity by cortexolone in alcoholic rats]. / Pozitivnaia moduliatsiia aktivnosti diazepama u alkogolizirovannykh krys pri pomoshchi korteksolona.

It has been shown that glucocorticoid receptor antagonist-cortexolone--increased anxiolytic action of diazepam in alcoholic rats. Neither diazepam (2 mg/kg), nor cortexolone (20 mg/kg) alone influenced voluntary ethanol consumption in alcoholic rats during 14 days of administration, however, combined administration of diazepam and cortexolone diminished ethanol consumption. Receptor and permissive mechanism of gluco- and antiglucocorticoid effect on the action of diazepam are being discussed.

[Cortexolone as a modulator of diazepam activity]. / Korteksolon kak moduliator aktivnosti diazepama.

The influence of ACTH (200 micrograms/kg), corticosterone (20 mg/kg) and cortexolone (20 mg/kg) on the anxiolytic activity of diazepam was studied. ACTH partly and corticosterone completely blocked the action of diazepam. Cortexolone injection 30 min before the administration of diazepam induced a 100% anxiolytic effect of diazepam in the range of doses from 0.1 to 0.3 mg/kg (ED50 of anxiolytic diazepam effect is 0.2 mg/kg). The role of stress hormones in the regulation of psychotropic drug activity is discussed.

Effect of chronic ethanol administration and abstinence on serum thyroid-stimulating hormone, prolactin and growth hormone concentrations in rats with high and low ethanol intake.

Serum anterior pituitary hormone levels of genetically selected AA and ANA rats of Wistar origin as well as those of experimentally selected heavy drinkers (HD) and light drinkers (LD) among normal Wistar rats were studied. AA and HD rats consumed high doses while ANA and LD rats preferred low doses of ethanol. Serum thyroid-stimulating hormone (TSH), prolactin and growth hormone (GH) concentrations were measured by specific radio-immuno-assays before chronic ethanol administration, during physical dependence and on subsequent withdrawal. Basal TSH levels and TSH responses to cold were as a rule decreased in the course of ethanol intake and abstinence, whereas the TRH-induced TSH elevation became more consistent than before ethanol. There was no difference in basal prolactin levels between ethanol preferring and non-preferring rats at abstinence, whereas 30 min cold-exposure seemed to decrease them in HD and LD rats. The high prolactin levels before ethanol and during physical dependence appear to be caused by stress factors involved in the blood collecting procedure. GH levels were not significantly different in ANA, AA, LD and HD rats and neither ethanol intake nor subsequent withdrawal consistently modified GH levels. It is concluded that the observed minor alterations in the levels of anterior pituitary hormones hardly play any significant role in the development of alcohol dependence.

[Types of alcoholic abstinence and the dexamethasone test]. / Tipy alkogol'noi abstinentsii i deksametazonovyi test.

The study covered 54 males with stage II alcoholism with various types of the abstinence syndrome in the state of acute abstinence (the first day of alcohol discontinuation) and 10 healthy males. The baseline cortisol levels were radioimmunoassayed and the dexamethasone suppression test (DST) was performed. The baseline levels of cortisol were elevated in all 4 types of the abstinence syndrome, being significantly higher in the dysphoric type. An abnormal DST was observed in 25 patients (46.3%) and was significantly more frequent in the depressive and schizothymovegetative types of the abstinence syndrome as against the asthenovegetative and dysphoric types and control. Psychometric examination revealed certain differences in the degree of abstinence symptoms and some clinical characteristics of the disease between patients with a pathologic and a normal DST.

[Changes in the gonadotropic function of the rat hypophysis during development of experimental alcoholism]. / Izmenenie gonadotropnoi funktsii gipofiza krys pri razvitii éksperimental'nogo alkogolizma.

Luteinizing hormone (LH) and prolactin blood plasma levels and LH level in the pituitary of alcoholic male rats were studied Alcoholic rats (heavy drinkers) have revealed hyperprolactinemia and inadequate LH secretions. The possible role of gonadotropins in the development of hypogonadism in alcoholic rats is discussed.

Types of alcohol withdrawal syndrome and dexamethasone suppression test.

Several data show a biological heterogeneity of the alcohol withdrawal syndrome. The determination of basic cortisol level and the Dexamethasone Suppression Test (DST) were performed in 10 healthy men and 54 male alcoholics in the stage of acute withdrawal divided into four groups, according to their clinical symptoms. In 46% of the patients the DST was positive (vs. nil in controls). The positive DST was significantly higher in subjects where depressive symptoms especially of endogenous character prevailed. The cortisol level was significantly increased in subjects characterized predominantly by anxiety-irritation. The possible explanations of these findings are discussed. The clinical picture of the withdrawal syndrome may be determined by disturbed functions of the hypothalamo-pituitary-adrenal system (HPAS). Correction of such disorders seems to be sufficient when treating acute withdrawal syndromes of different types.

[Effect of compounds with anxiolytic properties on voluntary ethanol consumption by rats]. / Vliianie soedinenii s anksioliticheskimi svoistvami na dobrovol'noe potreblenie étanola u krys.

The effect of different chemical anxiolytic agents on ethanol consumption has been studied on the model of experimental alcoholism in rats. The decrease of ethanol consumption was dose-dependent. The existence of non-benzodiazepine anxiolytic systems is suggested.

[Role of benzodiazepine receptors in realizing the anxiolytic effect of compounds on intact rats and on animals with a physical dependence ethanol]. / Rol' benzodiazepinovykh retseptorov v realizatsii anksioliticheskogo éffekta soedinenii u intaktnykh krys i u zhivotnykh s fizicheskoi zavisimost'iu ot étanola.

Anxiolytic activity of DSIP, sodium hydroxybutyrate, nicotinoyl-GABA, mebicar, some derivatives of aminoandrostane and beta-carboline was not, like in the case of diazepam and beta C-3CEE, related to benzodiazepine receptors. The degree of the decrease in anxiolytic activity of these compounds did not correspond to increasing Ki binding of 3H diazepam in alcoholic rats.

[Psychotropic properties of hormonally inactive derivatives of androstane]. / Nekotorye psikhotropnye svoistva gormonal'no neaktivnykh proizvodnykh androstana.

It has been shown in experiments on noninbred male rats that 17 beta-acetylamino-5-androstene-3 beta,16 beta-diol, 17 beta-amino-5-androstene-3 beta,16 beta-diol hydrochloride, and 17 beta-acetylamino-4-androstene-3,16-dione have an anxiolytic action. These compounds do not exhibit any myorelaxant, anticonvulsant or antineurotic activity common to benzodiazepine tranquilizers. The anxiolytic effect of the compounds under consideration is coupled with the ability to reduce the level of alcoholic motivation in rats.

[Anxiolytic action of beta-carbolines in rats]. / Anksioliticheskaia aktivnost' nekotorykh beta-karbolinov u krys.

The decreased sensitivity to the anxiolytic action of diazepam, BC-3-KEE, IME-6MEO-TGBC, IME-6MEO-DBC was shown in rats with experimental alcoholism. The degree of the decreased sensitivity was dependent on the affinity of the compounds to benzodiazepine receptors.

[Influence of thyroliberin and its analogs with different hormonal activity on the pharmacological effects of ethanol]. / Vliianie tiroliberina i ego analogov s razlichnoi gormonal'noi aktivnost'iu na nekotorye farmakologicheskie éffekty étanola.

TRH and its two analogs with modified hormonal activity were examined for the capacity to antagonize acute and chronic effects of ethanol in mice. It has been demonstrated that L-pyroglutamyl-L-seryl-L-leucinamide, an analog of TRH, that does not affect the secretion of TSH and decreases prolactin production has the same capacity as TRH to reduce the time of ethanol narcosis but produces a lesser effect on the ethanol-induced fall of rectal temperature. Both the drugs did not affect the ethanol-altered ability of mice to hold on the rotating bar. Methyl ether of TRH, a hormonally inactive analog, was ineffective as shown by all the tests. Neither TRH nor its analogs changed the development of tolerance to chronic administration of ethanol, recorded by the rotating bar test and rectal temperature drop.

[Role of endogenous sex steroids in the formation of experimental alcoholism in rats]. / Rol' éndogennykh polovykh steroidov v formirovanii éksperimental'-nogo alkogolizma u krys.

Depending on the duration of alcoholic narcosis white random-bred male rats predisposed and not predisposed to ethanol consumption manifested no differences in the content of androgens and estrogens in peripheral blood plasma. Ten-day voluntary alcoholization of the animals led to an abrupt reduction in testosterone concentration in blood plasma in much- and little-drinking rats. In the latter ones, that drop was more remarkable. In the course of the formation of the later stages of chronic alcoholism (12 months of voluntary alcoholization) the content of testosterone returned to normal in the group of little-drinking rats but remained slightly decreased in the much-drinking animals. The concentration of estradiol was unchanged in rats of all the test groups. However, the little-drinking animals showed insignificant hyperestrogenism after 12-month voluntary alcohol consumption.

[Enkephalins and gastrin fragments: possible existence of different analgesic mechanisms]. / Enkefaliny i fragmenty gastrina: vozmozhnost' sushchestvovaniia razlichnykh mekhanizmov anal'gezii.

The mechanism of analgetic action of pentagastrin, its tripeptide fragment (MAF), synthetic met- and leu-enkephalins was studied in rats. The analgetic effect of the peptides was evaluated from the tail extracting test. Also, the content of biogenic amines in the rat brain and interaction of the peptides with opiate receptors of the guinea-pig ileum were examined. It was demonstrated that analgesia induced by pentagastrin or MAF differs from that obtained after intraventricular injection of the enkephalins. The effect of the latter ones is not consequent on their interaction with classic opiate receptors. It was also discovered that pentagastrin, MAF and enkephalins produce a different action on metabolism of biogenic amines. The possibility of analgesia unmediated by specific peptide binding to opiate receptors is discussed.

[Relationship between the chief histocompatibility systems of mice and humans and predisposition to develop narcotic dependence]. / Sviaz' glavnoi sistemy gistosovmestimosti myshi i cheloveka s predraspolozhennost'iu organizma k razvitiiu narkoticheskoi zavisimosti.

Experiments on congenitally resistant lines of mice have demonstrated the relationship between H-2 haplotype and pronounced physical dependence in chronic morphine administration. Distribution of HLA-antigens was studied in a group of polynarcomanic patients who showed a significant increase in the occurrence of HLA-B5- and HLA-CW4-antigens. Potential use of these antigens as genetic markers of predisposition to narcotization is discussed.