The Significance of Toll-Like Receptors in the Neuroimmunologic Background of Alcohol Dependence

Toll-like receptors (TLR) are a group of protein belonging to the family of Pattern Recognition Receptors (PRR) which have the ability to distinguish between an organism's own antigens and foreign ones and to induce immunological response. TLR play a significant part in non-specific immunity but at the same time they are also a vital element linking non-specific response to the specific one. A growing number of data seems to indicate that the non-specific immunity mechanisms affect the development and sustenance of alcohol addiction. Alcohol damages the organism's cells not only directly but also through an increase inintestinal permeability which induces innate immune response of peripheral blood cells. The signaling pathway of Toll-like receptors located on the surface of brain immune cells intensifies the inflammatory reaction and, through modifying gene expression of proinflammatory factors, unnaturally supports it. This overly protracted “sterile inflammatory reaction” positively correlates with alcohol craving affecting also the functioning of the reward system structures and increasing the risk of relapse of alcoholism. Recurrent alcoholic binges sensitize the microglia and cause an escalation in inflammatory reaction which also leads to neurodegeneration. The induction of innate immunity signaling pathways exposes clinical symptoms of alcohol addiction such as increased impulsivity, loss of behavioral control, depressive-anxiety symptoms and cognitive dysfunctions. Traditional methods of treating alcohol addiction have tended to focus predominantly on reducing symptoms which—given the frequency of relapses—seems insufficient. The aim of the present paper is to discuss the role of toll-like receptors as elements of the immunity system which, together with the nervous system, plays a crucial part in the pathogenesis of alcohol addiction. We also wish to present pharmacotherapeutic perspectives targeted at the neuroimmunological mechanisms of alcohol addiction.

Addiction recovery stories: Jerome Carson in conversation with Lisa Ogilvie

Purpose The purpose of this paper is to explore the accomplishments of those who realise addiction recovery. To the best of the authors’ knowledge, this is the first in a series of recovery stories, where candid accounts of addiction and recovery are examined. In doing so, shared components of recovery are considered, along with the change and growth necessary to facilitate it. Design/methodology/approach The CHIME (Connectedness, Hope, Identity, Meaning and Empowerment) framework comprises five elements important to recovery. It provides a standard to qualitatively study mental health recovery, having also been applied to addiction recovery. In this paper, an additional element for Growth has been introduced to the model (G-CHIME), to consider both recovery and sustained recovery. A first-hand account of addiction recovery is presented, followed by a semi-structured e-interview with the author of the account. This is structured on the G-CHIME model. Findings This paper shows that successful and sustained recovery from alcohol addiction can be effectively explained using the G-CHIME model. Each element was well represented in the described process of reaching recovery. Originality/value Each account of recovery in this series is unique, and as yet, untold.

Alcoholism Among the Priests of the Đakovo-Osijek Archdiocese

In many countries today, alcoholism is becoming an increasingly common problem, the number of alcoholics is increasing, and the disease occurs in all professions and occupations. Therefore, it is important to talk about the increasing presence of alcoholism not only among lay believers but also among the clergy of the Catholic Church. The aim of this paper is to point out the causes of alcohol addiction and the consequences of alcoholism on the life and work of priests from the area of the Đakovo-Osijek Archdiocese. Based on the results of qualitative-quantitative research conducted using a survey questionnaire (9 priests), sampled using the »snowball« technique, this paper will, for the first time, talk about a problem that has not been discussed in the Croatian scientific community. The conducted research points to stressful events, loneliness, and mis-understanding of superiors and the environment as the main causes of alcoholism among priests.

Hypodopaminergic state of the nigrostriatal pathway drives compulsive alcohol use

The neurobiological mechanisms underlying compulsive alcohol use, a cardinal feature of alcohol use disorder, remain elusive even though they have often been suggested to involve dopamine (DA). Here, we found that rats expressing compulsive alcohol-related behavior, operationalized as punishment-resistant self-administration, showed a decrease in DA levels restricted to the dorsolateral territories of the striatum, the main output structure of the nigrostriatal DA pathway. We then causally demonstrated that a chemogenetic-induced selective hypodopaminergia of this pathway results in compulsive alcohol self-administration in rats otherwise resilient, accompanied by the emergence of alcohol withdrawal-like motivational impairments. These results demonstrate a major implication of tonic nigrostriatal hypodopaminergic state in alcohol addiction and provide new insights into our understanding of the neurobiological mechanisms underlying compulsive alcohol use.

Linking Ethanol-Addictive Behaviors With Brain Catecholamines: Release Pattern Matters

Using a variety of animal models that simulate key features of the alcohol use disorder (AUD), remarkable progress has been made in identifying neurochemical targets that may contribute to the development of alcohol addiction. In this search, the dopamine (DA) and norepinephrine (NE) systems have been long thought to play a leading role in comparison with other brain systems. However, just recent development and application of optogenetic approaches into the alcohol research field provided opportunity to identify neuronal circuits and specific patterns of neurotransmission that govern the key components of ethanol-addictive behaviors. This critical review summarizes earlier findings, which initially disclosed catecholamine substrates of ethanol actions in the brain and shows how the latest methodologies help us to reveal the significance of DA and NE release changes. Specifically, we focused on recent optogenetic investigations aimed to reveal cause-effect relationships between ethanol-drinking (seeking and taking) behaviors and catecholamine dynamics in distinct brain pathways. These studies gain the knowledge that is needed for the better understanding addiction mechanisms and, therefore, for development of more effective AUD treatments. Based on the reviewed findings, new messages for researches were indicated, which may have broad applications beyond the field of alcohol addiction.

Shame and Alcoholism in Paula Hawkins’s The Girl on the Train

The aim of this article is to showcase the connection between the portrayal of shame and alcohol addiction, on the one hand, and the mystery of murder and violence against women, on the other, in Paula Hawkins’s thriller The Girl on the Train (2015). This article argues that Hawkins’s book uses the thriller formula to reveal the links between gender and violence by delving into the vulnerability, suffering and resilience of the female characters through the stories of alcoholic troubled protagonist, Rachael Watson and the mystery of Megan Hipwell’s murder.

Variations of Brain Functional Connectivity in Alcohol-Preferring and Non-Preferring Rats with Consecutive Alcohol Training or Acute Alcohol Administration

Alcohol addiction is regarded as a series of dynamic changes to neural circuitries. A comparison of the global network during different stages of alcohol addiction could provide an efficient way to understand the neurobiological basis of addiction. Two animal models (P-rats screened from an alcohol preference family, and NP-rats screened from an alcohol non-preference family) were trained for alcohol preference with a two-bottle free choice method for 4 weeks. To examine the changes in the neural response to alcohol during the development of alcohol preference and acute stimulation, different trials were studied with resting-state fMRI methods during different periods of alcohol preference. The correlation coefficients of 28 regions in the whole brain were calculated, and the results were compared for alcohol preference related to the genetic background/training association. The variety of coherence patterns was highly related to the state and development of alcohol preference. We observed significant special brain connectivity changes during alcohol preference in P-rats. The comparison between the P- and NP-rats highlighted the role of genetic background in alcohol preference. The results of this study support the alterations of the neural network connection during the formation of alcohol preference and confirm that alcohol preference is highly related to the genetic background. This study could provide an effective approach for understanding the neurobiological basis of alcohol addiction.

Psychodynamic personal predictors of alcohol addiction propensity for lawenforcement officers

The article is devoted to the study of personality predictors of alcohol addiction propensity of internal affairs bodies employees within innovative psychodynamic G. Ammon’s (psychoanalytic) approach and structural-dynamic concept of personality. The novelty of the research is the original author’s psychodiagnostic toolkit – Psychodynamically oriented personality questionnaire (POLO) «Resource» and an expert psychodiagnostic system for assessing and predicting the professional psychological health of lawenforcers based on the assessment of central self-functions of the individual rooted in the unconscious. The relevance of the study is due to a significant number of violations of job discipline and legality. That includes accidents committed by employees while intoxicated, often with serious consequences and criminal prosecution, as well as the fairly widespread and concealed cases of alcohol addictions among lawenforcement officers. Another important factor is lack of effective methods of psychodiagnostics, psychocorrection and psychoprophylaxis. The study is based on a comparative analysis of 2 representative polar groups of internal affairs officers: the one verified prone and another of not prone to alcohol abuse. The study revealed that employees prone to alcohol addiction demonstrate a number of reliable psychodynamic personality characteristics that can be viewed as predictors: destructive aggression, deficit fear, deficient internal self-delimitation, as well as the general predominance of destructive-deficient components of the personal self-structure; indicators of psychosomatic, behavioral and neurotic maladaptation, and the integral scale of the general socio-psycho-somatic problem of POLO «Resource». The practical significance of the study is determined by the development of psychodynamic predictors and a special psychodiagnostic scale of propensity for alcohol addiction based on the Resource POLO, which can be used as an effective psychodiagnostic tool when conducting screening and monitoring psychoprophylactic examinations of employees and individual psychocorrectional work within the framework of the psychological support system of employees.

Histochemical characteristics of nitrergic neuronal system during acute alcohol intoxication and nNOS blockage in the rat lateral septum

Annotation. Alcohol is a one of the most frequently consumed substances of abuse, which can cause addiction or alcohol use disorders (AUDs). Alcohol addiction leads to decrease of the life quality of patients and considerable economic burden. Neuronal mechanisms of addiction are intensively studied. One of the most important systems involved in this process is a brain reward system that includes lateral septum (LS). Additionally alcohol consumption changes activity of the neurotransmitter systems including the nitric oxide (NO). Recent studies for blockage of nitric oxide synthase (NOS) for cocaine addiction and late stages of AUDs demonstrated that a group of the substances known as blockers of NOS can be referred to as candidates for alcohol addiction therapy. The aim of our research was to investigate histochemical characteristics of NO-system in LS, its response to acute alcohol intoxication including or excluding neuronal NOS (nNOS) blockage with selective inhibitor – 7-nitroindazole (7-NI). This study involved three experimental groups of animals (control group (n=4), group with acute alcohol intoxication (n=4), group of nNOS blockage with acute alcohol intoxication (n=4)). For statistical analysis, one-way Kruskal-Wallis test was implemented to reveal differences between groups (Matlab, Mathworks). We have identified NOS-positive structures in LS consisting of big neurons, medium/small neurons and nerve fibers. Acute alcohol intoxication activated subpopulations of NOS-positive medium/small neurons and nerve fibers. Moreover, we determined that ethanol-induced changes can be blocked with selective nNOS inhibitor 7-NI.