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Dynamics of the alcohol intake variation in MR and MNRA inbred rats with different emotional-stress reaction (ESR) phenotypes was studied in the course of a 7-month voluntary alcoholization. Initially, the MNRA rats with an active ESR phenotype showed a higher level of a 15% aqueous ethanol consumption than did the MR rats. After 3 months, the consumption of ethanol in the highly emotional MR rats sharply increased and was retained on a high level during subsequent alcoholization. The new anxiolytic agent afobazol [5-ethoxy-2(morpholinoethylthio)-benzimidazole hydrochliride] did not potentiate the CNS depressant action of alcohol. A 2-week administration of afobazol (1 mg/kg, i.p.) after a 6-month alcoholization markedly reduced the alcohol consumption and reduced the craving to alcohol in the rats of both lines studied.

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Hereditary variations in the effects of benzodiazepine tranquilizers depending on the phenotype of an emotional stress reaction (ESR) are described. The membrane-receptor relationship showed differences between C57B1/6 with an "active" ESR phenotype and Balb/c with a "passive" ESR at the GABA benzodiazepine receptor complex level. The pharmacological results evidenced the selective anxiolytic properties of the novel drug aphobazole (2-[2-morpholyno)ethylthio]-5-ethoxybenzimidazole dihydrochloride) which produced an activating anxiolytic action in Balb/c mice whereas no behavioral changes were observed in C57B1/6 mice.

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The effect of the new drug SM-346, a derivative of 2-mercaptobenzimidazole, on the behavior of inbred MR and MNRA rats, differing in the phenotype of the emotional-stress reaction in the open field test was studies. In the Vogel conflict test SM-346 in a dose of 1 mg/kg produced an anxiolytic effect in MR rats but had no effect on the behavior of MNRA rats. The obtained results allow the conclusion that SM-346 possesses a selective anxiolytic action.

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A set of correlating indices has been developed to assess alcohol craving in rats who has a free access to it for 24 months. The set includes the estimation of voluntary daily alcohol intake before and after ethanol deprivation and the assessment of rats' behavior in a conflict situation and a plus-maze. The increased intake of alcohol after its deprivation has been established to correlate with a number of punished ethanol lickings in the conflict paradigm and functional locomotor asymmetry in the plus-maze.

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In rats with the persistent alcohol motivation the electrophysiological sleep pattern was studied during ethanol intake, after 24 and 48 hours of alcohol withdrawal. It was established that during the voluntary ethanol intake rats may be divided into two groups: with comparative deficit (1st group) and comparative abundance (2nd group) of REM sleep. Alcohol withdrawal caused differential alterations of sleep-wakefulness cycle: in the 1st group of rats REM sleep was more suppressed while in the 2nd group--more increased in comparison to those during ethanol intake. In all animals the SWS depression, increase of awakenings, the aggravation of falling asleep and decrease of sleep depth were observed. DSIP (0.1 mg/kg, i.p. 1 hour before sleep recording) was found to regulate sleep disorders caused by ethanol withdrawal. It makes the neuropeptide possible to be recommended for ethanol withdrawal syndrome treatment in clinical practice.

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The express technique reflecting an acquisition of a clear alcohol addiction during short-term voluntary alcoholization for further antialcoholic drugs testing was performed in male albino rats. By VARIMAX factor analysis of indexes related with preference of alcohol solutions with different tastes the conditions of short-term (2 months) voluntary alcoholization leading to persistent ethanol intake were studied. Isolation stress inducing a specific alcohol drive was excluded from rearing conditions. 0.1% saccharin solution in 15% ethanol was used for alcoholization. Statistical analysis revealed factor of "developed alcohol abuse" which may be detected in conditions of one-trail sweet ethanol intake after 3 days alcohol deprivation (similar to heavy drinking syndrome in humans). Using pharmacological drugs (pyrazidol, piracetam) validity of the method for specific drug design was confirmed.

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In experiments on albino rats divided in to groups with different behavioral activity under stress situation ("high active" and "low active") it was shown that the "low active" animals differ from the "high active" ones by an increased rate of alcohol elimination, enhanced duration of the fast sleep phase, a tendency towards its reduction in response to a single administration of ethanol as well as a higher level of alcohol motivation.

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The initial threshold of pain sensitivity and the degree of morphine analgesia (12, 12, 70 mg/kg, i. p.) were assessed during mechanical, thermal and electrical stimulation, respectively, in noninbred white male mice. Two tests were performed, the second a week after the first one. A slight positive correlation (r = +0.39) between the initial threshold of pain reaction and the analgetic effect of morphine was found only during electrical stimulation in the first test, and positive correlation between the first and the second test during electrical and mechanical stimulation (0.34 and 0.27, respectively) was determined. The degree of morphine analgesia in different animals during second testing could either increase or decrease. It is suggested that previous testing of morphine analgetic effect cannot predict the efficacy of analgesia during the second testing and that the initial threshold of pain sensitivity cannot serve as a reliable predictor of morphine analgesia level.

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The consequences of self-stimulation reaction (RSS) to pain threshold in tail withdrawal test (55 degrees C) and naloxone effect have been investigated in tests, using male rats with chronically implanted electrodes into the hypothalamus (AP = 1.5, L = 1.5, H = 8.5) and suture dorsal nucleus (AP = 7.0, L = 0, H = 7.0) (coordinates according to Fifková atlas). It was established that right after RSS, pain threshold in both zones increased 2-2.5-fold and 30 min later reached the initial level. Naloxone injected before RSS increased pain thresholds and decreased RSS frequency from hypothalamus but failed to change these RSS parameters from suture dorsal nucleus. However, naloxone did not affect the increase in pain thresholds caused by RSS from both zones. Taking into account the fact that analgesia appearing after RSS from the anterior hypothalamus as well as from suture dorsal nucleus is not reversed by naloxone, it is suggested that positive reward zones activation partially realized by opioidergic mechanisms or having no connection with them may lead to the development of non-opiate type analgesia.

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Ethanol elimination from the blood of rats with different psychophysiological features was studied using gas chromatographic head-space analysis in the general complex of tests aimed at determination of ethanol consumption. The selection of animals with different levels of the initial alcohol motivation was performed according to modified Porsolt's method. It was shown that the initial level of predisposition to depression-like states is in a dose-dependent correlation with the high rate of ethanol elimination. This is suggested to be one of the genetic indications which promotes the formation of the initial alcohol motivation and the development of experimental alcoholism.

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Using modified Porsolt's method, the electrophysiological sleep pattern was studied in normal conditions and after a single intraperitoneal ethanol injection to noninbred male albino rats divided into 2 groups ("high activity" and "low activity" rats). Voluntary alcohol intake in these rats was measured during free choice between 10% ethanol and water for 20 days. "Low activity" rats were characterized by a statistically significant 3.4-fold higher level of ethanol consumption and 2.7-fold longer REM-sleep stage, as compared to "high activity" animals. In "low activity" animals ethanol (1 g/k, 10% solution, i. p.) inhibits and in "high activity" rats it increases REM-sleep stage, thus removing differences in the sleep pattern in the two groups of rats. The data obtained suggest a possible role of REM-sleep in the development of alcohol motivation.

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The effects of sodium hydroxybutyrate (100 mg/kg); phenazepam (1 mg/kg), apomorphine (0.1 mg/kg and haloperidol (1 mg/kg) on the electrophysiological sleep pattern were studied in rats during 7-day alcohol withdrawal after its voluntary consumption for 13 months. It was shown that alcohol withdrawal led to profound disorders in the sleep-waking cycle. Sodium hydroxybutyrate prevented these disturbances and brought sleep to normal. Phenazepam exerted a powerful sedative and hypnotic effects but did not improve the balance of sleep phases. Apomorphine displayed a tendency to sleep normalization. However, this effect was short-term. Haloperidol did not eliminate abstinence manifestations in the sleep pattern.

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