Neuroimmune and Mu-Opioid Receptor Alterations in the Mesocorticolimbic System in a Sex-Dependent Inflammatory Pain-Induced Alcohol Relapse-Like Rat Model.

Evidence concerning the role of alcohol-induced neuroinflammation in alcohol intake and relapse has increased in the last few years. It is also proven that mu-opioid receptors (MORs) mediate the reinforcing properties of alcohol and, interestingly, previous research suggests that neuroinflammation and MORs could be related. Our objective is to study neuroinflammatory states and microglial activation, together with adaptations on MOR expression in the mesocorticolimbic system (MCLS) during the abstinence and relapse phases. To do so, we have used a sex-dependent rat model of complete Freund's adjuvant (CFA)-induced alcohol deprivation effect (ADE). Firstly, our results confirm that only CFA-treated female rats, the only experimental group that showed relapse-like behavior, exhibited specific alterations in the expression of phosphorylated NFκB, iNOS, and COX2 in the PFC and VTA. More interestingly, the analysis of the IBA1 expression revealed a decrease of the microglial activation in PFC during abstinence and an increase of its expression in the relapse phase, together with an augmentation of this activation in the NAc in both phases that only occur in female CFA-treated rats. Additionally, the expression of IL1ß also evidenced these dynamic changes through these two phases following similar expression patterns in both areas. Furthermore, the expression of the cytokine IL10 showed a different profile than that of IL1ß, indicating anti-inflammatory processes occurring only during abstinence in the PFC of CFA-female rats but neither during the reintroduction phase in PFC nor in the NAc. These data indicate a downregulation of microglial activation and pro-inflammatory processes during abstinence in the PFC, whereas an upregulation can be observed in the NAc during abstinence that is maintained during the reintroduction phase only in CFA-female rats. Secondly, our data reveal a correlation between the alterations observed in IL1ß, IBA1 levels, and MOR levels in the PFC and NAc of CFA-treated female rats. Although premature, our data suggest that neuroinflammatory processes, together with neural adaptations involving MOR, might play an important role in alcohol relapse in female rats, so further investigations are warranted.

Stress-related suppression of peripheral cytokines predicts future relapse in alcohol-dependent individuals with and without subclinical depression.

Chronic alcohol abuse and depressive symptoms are both associated with peripheral cytokine changes. Despite this, cytokine adaptations have not been assessed in co-morbid populations or prospectively as predictors of relapse. We examine cytokine responses to stress in alcohol-dependent individuals and social drinkers, both with and without subclinical depression. We also examine the potential link between cytokine adaptations in response to stress and prospective alcohol relapse risk. Thirty-three, alcohol-dependent individuals (21 with and 12 without high depressive symptoms) and 37 controls (16 with and 21 without high depressive symptoms) were exposed to two 5-minute personalized guided imagery conditions (stress and neutral) across consecutive days in a randomized and counterbalanced order. Alcohol craving and serum measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) were collected prior to and following imagery exposure. Following treatment discharge, follow-up interviews were conducted over 90 days to assess relapse. Dampened IL-1ra and IL-6 in response to stress was observed as a function of alcohol dependence and not moderated by depressive symptoms. Lower levels of IL-6 following stress also predicted greater drinking days following treatment. Conversely, high depressive symptomatology was associated solely with pro-inflammatory adaptations. Stress-related suppression of TNFα predicted drinking severity only in alcohol-dependent individuals with subclinical depression, and suppressed TNFR1 following stress was only seen in individuals with subclinical depression. Stress-induced suppression of pro-inflammatory TNF markers may indicate a risk factor for alcohol-dependent individuals with co-occurring depressive symptoms.

Alcohol or Gut Microbiota: Who Is the Guilty?

Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.

Peripheral immune system suppression in early abstinent alcohol-dependent individuals: Links to stress and cue-related craving.

BACKGROUND: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. METHODS: A total of 39 early abstinent, treatment-seeking, alcohol-dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. RESULTS: The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also showed a dampened TNFα and TNFR1 response to stress and cue, respectively, and a generalized suppression of IL-6. In the alcohol group, these immune system adaptations occurred alongside significant elevations in anxiety, negative mood and alcohol craving. CONCLUSIONS: Findings demonstrate that broad immunosuppression is still observed in alcohol-dependent individuals after 3 weeks of abstinence and may be linked to motivation for alcohol.

Mechanisms of neuroimmune gene induction in alcoholism.

RATIONALE: Alcoholism is a primary, chronic relapsing disease of brain reward, motivation, memory, and related circuitry. It is characterized by an individual's continued drinking despite negative consequences related to alcohol use, which is exemplified by alcohol use leading to clinically significant impairment or distress. Chronic alcohol consumption increases the expression of innate immune signaling molecules (ISMs) in the brain that alter cognitive processes and promote alcohol drinking. OBJECTIVES: Unraveling the mechanisms of alcohol-induced neuroimmune gene induction is complicated by positive loops of multiple cytokines and other signaling molecules that converge on nuclear factor kappa-light-chain-enhancer of activated B cells and activator protein-1 leading to induction of additional neuroimmune signaling molecules that amplify and expand the expression of ISMs. RESULTS: Studies from our laboratory employing reverse transcription polymerase chain reaction (RT-PCR) to assess mRNA, immunohistochemistry and Western blot analysis to assess protein expression, and others suggest that ethanol increases brain neuroimmune gene and protein expression through two distinct mechanisms involving (1) systemic induction of innate immune molecules that are transported from blood to the brain and (2) the direct release of high-mobility group box 1 (HMGB1) from neurons in the brain. Released HMGB1 signals through multiple receptors, particularly Toll-like receptor (TLR) 4, that potentiate cytokine receptor responses leading to a hyperexcitable state that disrupts neuronal networks and increases excitotoxic neuronal death. Innate immune gene activation in brain is persistent, consistent with the chronic relapsing disease that is alcoholism. Expression of HMGB1, TLRs, and other ISMs is increased several-fold in the human orbital frontal cortex, and expression of these molecules is highly correlated with each other as well as lifetime alcohol consumption and age of drinking onset. CONCLUSIONS: The persistent and cumulative nature of alcohol on HMGB1 and TLR gene induction support their involvement in alcohol-induced long-term changes in brain function and neurodegeneration.

Alcoholism causes alveolar macrophage zinc deficiency and immune dysfunction.

RATIONALE: Alcohol use disorders cause oxidative stress in the lower airways and increase susceptibility to pneumonia and lung injury. Currently, no therapeutic options exist to mitigate the pulmonary consequences of alcoholism. OBJECTIVES: We recently determined in an animal model that alcohol ingestion impairs pulmonary zinc metabolism and causes alveolar macrophage immune dysfunction. The objective of this research is to determine the effects of alcoholism on zinc bioavailability and alveolar macrophage function in human subjects. METHODS: We recruited otherwise healthy alcoholics (n = 17) and matched control subjects (n = 17) who underwent bronchoscopy for isolation of alveolar macrophages, which were analyzed for intracellular zinc, phagocytic function, and surface expression of granulocyte-macrophage colony-stimulating factor receptor; all three of these indices are decreased in experimental models. MEASUREMENTS AND MAIN RESULTS: Alcoholic subjects had normal serum zinc, but significantly decreased alveolar macrophage intracellular zinc levels (adjusted means [SE], 718 [41] vs. 948 [25] RFU/cell; P < 0.0001); bacterial phagocytosis (adjusted means [SE], 1,027 [48] vs. 1,509 [76] RFU/cell; P < 0.0001); and expression of granulocyte-macrophage colony-stimulating factor receptor ß subunit (adjusted means [SE], 1,471 [42] vs. 2,114 [35] RFU/cell; P < 0.0001]. Treating alveolar macrophages with zinc acetate and glutathione in vitro increased intracellular zinc levels and improved their phagocytic function. CONCLUSIONS: These novel clinical findings provide evidence that alcohol abuse is associated with significant zinc deficiency and immune dysfunction within the alveolar space and suggest that dietary supplementation with zinc and glutathione precursors could enhance airway innate immunity and decrease the risk for pneumonia or lung injury in these vulnerable individuals.

Spontaneous and in vitro induced apoptosis of lymphocytes and neutrophils in patients with alcohol dependence.

Spontaneous and induced apoptosis of neutrophils and lymphocytes was studied in alcoholics during the abstinent syndrome and in healthy individuals. In alcoholics, the levels of lymphocyte and neutrophil apoptosis at the receptor and cellular levels were higher than in healthy subjects. Blood cells from alcohol addicts and normal individuals similarly react to stimuli (hyperthermia and synthetic glucocorticoid prednisolone) in vitro.

Zinc deficiency mediates alcohol-induced alveolar epithelial and macrophage dysfunction in rats.

Chronic alcohol abuse impairs both alveolar epithelial and macrophage function, and renders individuals susceptible to acute lung injury, pneumonia, and other serious lung diseases. Zinc deficiency, which is known to impact both epithelial and immune cell functions, is also associated with alcohol abuse. In this study, chronic alcohol ingestion (6 wk) in rats altered expression of key zinc transporters and storage proteins in the small intestine and the lung, and decreased zinc levels in the alveolar compartment. Zinc supplementation of alveolar epithelial monolayers derived from alcohol-fed rats in vitro, or of the diets of alcohol-fed rats in vivo, restored alveolar epithelial barrier function, and these improvements were associated with salutary changes in tight junction protein expression and membrane localization. In parallel, dietary zinc supplementation increased intracellular zinc levels, GM-CSF receptor expression, and bacterial phagocytic capacity in the alveolar macrophages of alcohol-fed rats. Together, these studies implicate zinc deficiency as a novel mechanism mediating alcohol-induced alveolar epithelial and macrophage dysfunction. Importantly, these findings argue that dietary supplementation can overcome alcohol-induced zinc deficiency and restore alveolar epithelial and macrophage function, and therefore could be an effective treatment for the susceptible alcoholic lung phenotype.

A role for spiritual change in the benefits of 12-step involvement.

BACKGROUND: Emerging evidence implies a role for spirituality in recovery from substance abuse. The current study examines the hypothesis that spiritual change helps mediate (or explain) effects for involvement in 12-step groups on recovery outcomes among substance-abusing populations. METHODS: Participants (baseline N = 733) received treatment at 1 of 5 day hospital and 7 residential substance abuse treatment programs in California. Assessments included a baseline interview and 1-year follow-up; analyses incorporated regressions informed by Baron and Kenny (1986) and Sobel's (1982) test. To assess spirituality, measures included (1) the Religious Background and Behaviors scale and (2) an item assessing whether or not participants had had a spiritual awakening through their involvement with 12-step groups. RESULTS: Results confirmed the hypothesis. Increases in 12-step involvement from baseline to follow-up predicted higher odds of total abstinence at follow-up, and this relationship was partially explained by increases in spirituality. Results held in multivariate analyses and regardless of which spirituality measure was analyzed. CONCLUSIONS: The present study provides further evidence that spiritual change contributes to recovery, at least within the context of 12-step involvement. The study also deepens our understanding of how 12-step involvement works.

Naltrexone inhibits alcohol-mediated enhancement of HIV infection of T lymphocytes.

Acute and chronic alcohol abuse impairs various functions of the immune system and thus, has been implicated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease progression. We determined whether naltrexone, an opioid receptor antagonist widely used in the treatment of alcoholism, inhibits alcohol-mediated enhancement of HIV infection of T cells. Alcohol enhanced HIV infection of peripheral blood lymphocytes (PBL) and a human lymphoid cell line (CEMX174). Alcohol increased HIV X4 envelope (Env), not murine leukemia virus Env-pseudotyped infection of CEMX174 cells. Naltrexone antagonized the enhancing effect of alcohol on HIV infection of PBL and CEMX174 cells. The specific mu-opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7 (CTAP) amide, also blocked the enhancing effect of alcohol on HIV infection. Investigation of the underlying mechanism for the alcohol action showed that alcohol significantly increased endogenous beta-endorphin production and induced mu-opioid receptor mRNA expression in PBL and CEMX174 cells. The role of beta-endorphin in alcohol-mediated enhancement of HIV infection was indicated by the observations that naltrexone and CTAP antagonized ether alcohol- or exogenous beta-endorphin-mediated enhancement of HIV infection. These findings suggest a biological mechanism for the potential therapeutic benefit of naltrexone in treating HIV-infected alcoholics.

Prolonged exposure to intermittent alcohol vapors blunts hypothalamic responsiveness to immune and non-immune signals.

BACKGROUND: We have previously shown that long-term alcohol treatment blunts the ACTH response to alcohol itself, as well as to other stresses, and is accompanied by decreased pituitary responsiveness to vasopressin (VP), but not corticotropin-releasing factor (CRF). The present work aims to determine the relevance of changes in CRF and VP receptors in the pituitary gland and/or peptide stores of CRF neurons in the paraventricular nucleus (PVN) of the hypothalamus, the areas that are most directly involved in ACTH release. METHODS: Intact male rats were exposed to alcohol using a new vapor delivery system which enables individual rat housing in boxes. Alcohol treatment was delivered for 6 hr once daily (0700-1300), after which the rats were returned to their home cages where they had free access to food and water. Control rats were kept in similar boxes, but not exposed to alcohol. Total treatment time was 8 days. All animals were equipped with indwelling jugular cannulae that were used to monitor blood alcohol levels (BALs) as well as ACTH and corticosterone release throughout drug exposure. Due to the presence of a swivel, the animals' movements were not restricted or hindered by the presence of these cannulae. On the morning of day 9, the animals were decapitated under basal conditions or exposed to a neurogenic (mild electrofootshocks) or systemic [i.v. lipopolysaccharide (LPS)] stimulus. PVN neuronal responses, indicated by changes in mRNA concentrations of the immediate early genes (IEGs) c-fos and NGFI-B, and plasma ACTH levels were measured before and during endotoxemia or electrofootshocks. RESULTS: In the absence of alcohol, plasma ACTH and corticosterone remained at basal levels, indicating the absence of environment-induced stress. In rats exposed to alcohol, BALs were consistent and predictable, and we targeted peak values of about 200 mg%. At the end of the drug treatment period, there were no significant differences between CRF and VP receptor mRNA levels in the anterior pituitary of control and alcohol-treated rats. In contrast, alcohol treatment respectively decreased CRF and increased VP stores in the external zone of the median eminence. It also increased NGFI-B and c-fos transcripts in the magnocellular (m) portion of the PVN, but not the parvicellular (p) division of this nucleus under basal conditions (i.e., in the absence of shocks or LPS). After exposure to these stressors, on the other hand, all groups of rats showed significant increases in plasma ACTH levels as well as up-regulation of their PVN neuronal response, as indicated by changes in pPVN IEGs transcripts. However, these hormonal and neuronal responses were significantly blunted in animals pretreated with alcohol. CONCLUSIONS: Collectively, our results suggest that decreased PVN neuronal activation represents an important mechanism of the ability of long-term alcohol treatment to blunt the ACTH response to shocks or endotoxemia. In addition, the new system of alcohol delivery that we developed is practical and reliable, and has the significant advantage that it enables measurement of circulating hormone levels during drug exposure of the animals.

Alterations in mouse Peyer's patch lymphocyte phenotype after ethanol consumption.

The objective of this study was to determine if chronic ethanol consumption could modify cell populations in the Peyer's patches (PP), which could favor pathogenic or opportunistic infections in mice, as seen in chronic alcohol addicts. Young C57BL/6 mice receiving the Lieber-DeCarli diet (36% of calories as ethanol) for 5 weeks presented a significant decrease in the total number of cells in the PP. Mature FVB mice receiving the Lieber-DeCarli diet for 19 weeks presented a highly significant decrease in the total number of cells and in the absolute number of T and B cells in the PP. Young C57BL/6 mice receiving the 100% NRC (30% ethanol) or the 60% NRC (30% ethanol) diets for 7 weeks presented alterations in the T and B cell phenotype comparable with the alterations observed in mice receiving the Lieber-DeCarli diet for 19 weeks. As less alcohol for a shorter time caused similar changes to those seen with a highly micronutrient enriched diet with more alcohol for a longer consumption period, micronutrient supplementation may overcome some immune damage found in animal models of alcoholism. Our data indicated that ethanol administration altered the mucosal immune system at the level of the PP, the site for antigen presentation and induction of a mucosal immune response.

[Alcohol and free radicals: from basic research to clinical prospects]. / Alcool et radicaux libres: de la recherche fondamentale aux espoirs cliniques.

An oxidative stress occurs in the liver of rats following various conditions of ethanol administration. The ethanol-inducible cytochrome P450 2E1 plays a key role in its generation, favoured itself by an increase in the "redox-active" fraction of intracellular non-heme iron. Administration of ethanol elicits the generation of the 1-hydroxyethyl radical, which has been identified in vivo. Its reactivity contributes to alcohol-induced immunological disturbances. Liver inflammatory and fibrotic disorders can be reproduced in rats by long-term ethanol administration associated with a high fat diet. The severity of these disorders is correlated to the intensity of the oxidative stress. Some conditions of ethanol administration to rats also elicit an oxidative stress in the myocardium and central nervous system. Through its inhibitory effect on glutamine synthetase activity and resulting excitotoxicity it may contribute to neuronal death and possibly to dependence on alcohol. Disorders related to an oxidative stress were also reported in the serum and erythrocytes as well as in liver biopsies from alcoholic individuals. Their detection may be useful to follow the evolution of alcoholic liver diseases. Supplementation with antioxidants such as vitamin E may be considered in the prevention of severe cellular disorders in individuals consuming large amounts of alcoholic beverages. An increase in free radical production is likely playing a role in the induction of severe cellular damage linked to repeated withdrawals occurring as a result of heavy and sporadic ethanol intake.

[The evaluation of the effect of zinc sulfate on primary immune response indices under alcoholic intoxication]. / Otsenka vliianiia sul'fata tsinka na pokazateli pervichnogo immunnogo otveta v usloviiakh alkogol'noi intoksikatsii.

Introduction of zinc sulfate in the composition of drinking liquid on the background of alcohol intoxication of animals increases the intensity of primary immune response to the sheep erythrocytes (ShE). This effect is manifested through an increase in the number of phagocytosing lymphocytes in peripheral blood, antibody forming cells in the spleen, antibody titer to ShE, and in an increase in the rosette-forming ability of lymphocytes. The data obtained indicate to the potential use of the zinc salts for immunity correction in conditions of chronic alcohol intoxication.

Immunomodulation by pycnogenol in retrovirus-infected or ethanol-fed mice.

Pycnogenol is a commercial mixture of bioflavonoids that exhibits antioxidative activity. The effects of dietary pycnogenol on immune dysfunction in normal mice as well as those fed ethanol or infected with the LP-BM5 murine retrovirus were determined. The ethanol consumption and retrovirus infection caused abnormalities in the function and/or structure of a broad array of cells involved in humoral and cellular immunity. Pycnogenol enhanced in vitro IL-2 production by mitogen-stimulated splenocytes if its production was suppressed in ethanol-fed or retrovirus-infected mice. Mitogenesis of splenocytes did not show a significant change in mice treated with pycnogenol. It reduced the elevated levels of interleukin-6 produced in vitro by cells from retrovirus infected mice and IL-10 secreted by spleen cells from mice consuming ethanol. Natural killer cell cytotoxicity was increased with pycnogenol treatment.

Dietary vitamin E modulation of cytokine production by splenocytes and thymocytes from alcohol-fed mice.

As vitamin E enhances immune responses, it may reduce dietary ethanol (EtOH)-induced immune suppression, thereby favorably affecting host disease resistance. The effects of dietary vitamin E at higher level in alcohol-fed female C57BL/6 mice was determined via in vitro cytokine production by splenocytes and thymocytes, and some other immune functions. A 15-fold increase of vitamin E (160 IU/liter) in a liquid diet (National Council Research), with or without EtOH (4.5%, v/v), was fed to mice for 10 weeks. Vitamin E supplementation restored production of interleukin-2, -5, -6, -10, and interferon-gamma by concanavalin A (Con A)-stimulated splenocytes and interleukin-6 and tumor necrosis factor-alpha by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. However, it had no effect on interleukin-4 secretion, which was also reduced by splenocytes from EtOH-fed mice. Vitamin E supplementation also restored EtOH-suppressed, mitogen-induced splenocyte proliferation, but not thymocyte proliferation, although it slightly increased production of immunoglobulin A and G by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. Dietary vitamin E, furthermore, significantly increased interleukin-2 and -6 secretion by Con A-stimulated thymocytes, which were suppressed by dietary EtOH, although it had no effect on interleukin-4 and interferon-gamma production by Con A-stimulated thymocytes from EtOH-fed mice. These data suggest that dietary vitamin E supplementation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion.

Ethanol, immune responses, and murine AIDS: the role of vitamin E as an immunostimulant and antioxidant.

Excessive alcohol consumption is a major health problem in the United States. Prolonged consumption of alcohol results in alterations of immune responses, ultimately manifested by increasing susceptibility to infectious agents. Such changes can be due to the direct effects of alcohol or its metabolites on immune cells, as well as to nutritional deficiency, oxidative stress, and neutrophil dysfunctions. This ETOH-induced immunosuppression could be a potential cofactor in the progression to AIDS. As vitamin E supplementation has been associated with enhancement of immune response and improvement of host defense, it may provide a useful therapeutic approach for treatment of alcoholics to improve host defense. This article is a review of alcohol-related immunosuppression as a possible cofactor in the development of AIDS, and vitamin E-related immunoenhancing roles in animals and humans, showing why vitamin E supplementation could be used as a useful adjunct agent in alcoholics' treatment. Since there is little information available regarding nutritional therapy with alcohol users, our purpose is to provide evidence from animal models of the potential therapeutic role of vitamin E supplementation in the treatment of alcoholics.

Increased natural killer cell activity in a model of immunoglobulin A nephropathy secondary to chronic alcohol consumption.

We investigated natural killer (NK) cell activity in an animal model of ethanol-induced immunoglobulin A (IgA) nephropathy. Two groups, of 10 rats each, received a continuous intragastric infusion of liquid diet through a permanent cannula for 6 weeks. The alcoholic group was infused additionally with intragastric ethanol, representing from 32% to 40% of the caloric requirement. The group of control rats received an isocaloric diet supplemented with glucose instead of alcohol. IgA nephropathy was observed in all the alcoholic rats but in none of the controls. NK cell activity was investigated in the two groups by measuring the cytotoxicity of spleen cells using the chromium release method. NK cell activity was found to be significantly increased in the alcoholic rats. In view of the known modulation of IgA synthesis by NK cells, we suggest that increased NK cell activity may be a contributing factor to the high levels of circulating IgA seen in IgA nephropathy secondary to chronic alcohol consumption.

[The immunization of white rats with a covalent conjugate of sidnofen and serum albumin suppresses chronic ethanol consumption]. / Immunizatsiia belykh krys kovalentnym kon''iugatom sidnofena s serumal'buminom podavliaet khronicheskoe potreblenie étanola.

The influence of white rats of alcohol abuse formation of immunization by covalent conjugates of serum albumin with psychostimulant sydnophen was investigated. Immunization by conjugates where the molar sydnophen: protein ratio was 18:1-33: 1 results in significant depression of 15% ethanol consumption (in the condition of free choice between water and ethanol solution).