scholarly journals Hypodopaminergic state of the nigrostriatal pathway drives compulsive alcohol use

2021 ◽  
Author(s):  
Raphael Goutaudier ◽  
David Mallet ◽  
Magali Bartolomucci ◽  
Carole Carcenac ◽  
Frédérique Vossier ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Alcohol Addiction ◽  
Nigrostriatal Pathway ◽  
Self Administration ◽  
Output Structure ◽  
Major Implication ◽  
Cardinal Feature

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.

scholarly journals Sugar intake and craving during alcohol withdrawal in alcohol use disorder inpatients

2020 ◽  
Author(s):  
Régis Alarcon ◽  
Margaux Tiberghien ◽  
Raphael Trouillet ◽  
Stéphanie Pelletier ◽  
Amandine Luquiens ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Sugar Intake

Psychopharmacology for Substance Use Disorders

2021 ◽  
Author(s):  
Olapeju Simoyan ◽  
Krista Ulisse
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Maintenance Treatment ◽  
The United States ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Duration Of Symptoms ◽  
Stimulant Use

The illicit use of opioids is the fastest growing substance use problem in the United States. There are three FDA- approved medications for maintenance treatment for opioid use disorder: methadone, buprenorphine and naltrexone. Stimulants include cocaine and methamphetamines. 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) is an amphetamine derivative that also has hallucinogenic properties. Treatment of stimulant withdrawal is primarily supportive. Psychosocial interventions for stimulant use disorder may improve adherence, but they have not been shown to improve abstinence at the end of treatment. Benzodiazepines have been shown to reduce the severity and duration of symptoms related to alcohol withdrawal, in addition to reducing the risk of seizures. The Food and Drug Administration has approved disulfiram, acamprosate and naltrexone for the treatment of alcohol use disorder. This review contains 3 tables, and 31 references. Keywords: Opioid use disorder, maintenance treatment for opioid use disorder, stimulant use disorder, stimulant withdrawal, benzodiazepine overdose, benzodiazepine withdrawal, alcohol use disorder, alcohol withdrawal

Alcohol withdrawal symptoms predict corticostriatal dysfunction that is reversed by prazosin treatment in alcohol use disorder

2021 ◽  
Author(s):  
Rajita Sinha ◽  
Nia Fogelman ◽  
Stephanie Wemm ◽  
Gustavo Angarita ◽  
Dongju Seo ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Withdrawal Symptoms

scholarly journals Behavioral, Emotional and Social Apathy in Alcohol-Related Cognitive Disorders

2021 ◽  
Vol 10 (11) ◽  
pp. 2447
Author(s):  
Maud E. G. van Dorst ◽  
Yvonne C. M. Rensen ◽  
Masud Husain ◽  
Roy P. C. Kessels
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Cognitive Impairments ◽  
Cognitive Disorders ◽  
Neuropsychiatric Symptom ◽  
Alcohol Addiction ◽  
Substantial Proportion ◽  
Everyday Functioning ◽  
Prominent Symptom ◽  
Patient Groups

Apathy is a fundamental neuropsychiatric symptom of Korsakoff’s syndrome (KS) and has also been reported in patients with alcohol use disorder with no (AUD) or less severe cognitive impairments (ARCI). However, research on the nature of apathy is limited in these groups. Aim of this study was to examine the multidimensional nature of apathy in patients with KS, ARCI and AUD. Moreover, we examined differences between apathy ratings by patients and their professional caregivers, and related apathy to everyday functioning and overall cognition. Twenty-five patients with KS, 25 patients with ARCI and 23 patients with AUD participated in this study. Apathy was measured using the apathy motivation index (AMI), which distinguishes behavioral, emotional and social apathy. Both patients and professional caregivers reported social apathy as the most prominent symptom, compared to behavioral and emotional apathy. Apathy ratings did not differ across the three patient groups. Discrepancies between patient and caregiver ratings were observed in patients with KS and ARCI, with more severe apathy reported by caregivers. Caregiver-reported behavioral and social, but not emotional, apathy was related to everyday functioning. These results show that apathy is present in a substantial proportion of patients with alcohol addiction with or without cognitive impairments.

scholarly journals Virtual Morris task responses in individuals in an abstinence phase from alcohol

2018 ◽  
Vol 96 (2) ◽  
pp. 128-136 ◽  
Author(s):  
Mauro Ceccanti ◽  
Giovanna Coriale ◽  
Derek A. Hamilton ◽  
Valentina Carito ◽  
Roberto Coccurello ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Spatial Learning ◽  
Probe Trial ◽  
Alcohol Use Disorder ◽  
Alcohol Addiction ◽  
Spatial Learning And Memory ◽  
Spatial Behaviour ◽  
Learning Tasks ◽  
History Of ◽  
Visible Condition

The present study was aimed at examining spatial learning and memory, in 33 men and 12 women with alcohol use disorder (AUD) undergoing ethanol detoxification, by using a virtual Morris task. As controls, we recruited 29 men and 10 women among episodic drinkers without a history of alcohol addiction or alcohol-related diseases. Elevated latency to the first movement in all trials was observed only in AUD persons; furthermore, control women had longer latencies compared with control men. Increased time spent to reach the hidden platform in the learning phase was found for women of both groups compared with men, in particular during trial 3. As predicted, AUD persons (more evident in men) spent less time in the target quadrant during the probe trial; however, AUD women had longer latencies to reach the platform in the visible condition during trials 6 and 7 that resulted in a greater distance moved. As for the probe trial, men of both groups showed increased virtual locomotion compared with the women of both groups. The present investigation confirms and extends previous studies showing (i) different gender responses in spatial learning tasks, (ii) some alterations due to alcohol addiction in virtual spatial learning, and (iii) differences between AUD men and AUD women in spatial-behaviour-related paradigms.

scholarly journals Leveraging genetic data to investigate molecular targets and drug repurposing candidates for treating alcohol use disorder and hepatotoxicity

2019 ◽  
Author(s):  
Joshua C. Gray ◽  
Mikela Murphy ◽  
Lorenzo Leggio
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Liver Function ◽  
Protein Interactions ◽  
Alcohol Use Disorder ◽  
Molecular Targets ◽  
Drug Repurposing ◽  
Protein Interaction Data ◽  
Self Administration ◽  
Risk Genes

AbstractBackgroundNovel treatments for alcohol use disorder (AUD) and alcohol-related liver disease (ALD) are greatly needed. Genetic information can improve drug discovery rates by facilitating the identification of novel biological targets and potential drugs for repurposing.MethodsThe present study utilized a recently developed Bayesian approach, Integrative Risk Gene Selector (iRIGS), to identify additional risk genes for alcohol consumption using SNPs from the largest alcohol consumption GWAS to date (N = 941,280). iRIGS incorporates several genomic features and closeness of these genes in network space to compute a posterior probability for protein coding genes near each SNP. We subsequently used the Target Central Resource Database to search for drug-protein interactions for these newly identified genes and previously identified risk genes for alcohol consumption.ResultsWe identified several genes that are novel contributions to the previously published alcohol consumption GWAS. Namely, ACVR2A, which is critical for liver function and linked to anxiety and cocaine self-administration, and PRKCE, which has been linked to alcohol self-administration. Notably, only a minority of the SNPs (18.4%) were linked to genes with confidence (≥.75), underscoring the need to apply multiple methods to assign function to loci. Finally, several previously identified risk genes for alcohol consumption code for proteins that are implicated in liver function and are targeted by drugs that are promising candidates for managing hepatotoxicity (e.g., metformin).ConclusionsThis study demonstrates the value of incorporating regulatory information and drug-protein interaction data to highlight additional molecular targets and drug repurposing candidates for treating AUD and ALD.

scholarly journals The effect of alcohol withdrawal syndrome severity on sleep, brain and cognition

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Alice Laniepce ◽  
Nicolas Cabé ◽  
Claire André ◽  
Françoise Bertran ◽  
Céline Boudehent ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Sleep Quality ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Use Disorder ◽  
Grey Matter ◽  
Short Term Memory ◽  
Alcohol Withdrawal Syndrome ◽  
Healthy Controls ◽  
Sleep Alterations

Abstract In alcohol use disorder, drinking cessation is frequently associated with an alcohol withdrawal syndrome. Early in abstinence (within the first 2 months after drinking cessation), when patients do not exhibit physical signs of alcohol withdrawal syndrome anymore (such as nausea, tremor or anxiety), studies report various brain, sleep and cognitive alterations, highly heterogeneous from one patient to another. While the acute neurotoxicity of alcohol withdrawal syndrome is well-known, its contribution to structural brain alterations, sleep disturbances and neuropsychological deficits observed early in abstinence has never been investigated and is addressed in this study. We included 54 alcohol use disorder patients early in abstinence (from 4 to 21 days of sobriety) and 50 healthy controls. When acute physical signs of alcohol withdrawal syndrome were no longer present, patients performed a detailed neuropsychological assessment, a T1-weighted MRI and a polysomnography for a subgroup of patients. According to the severity of the clinical symptoms collected during the acute withdrawal period, patients were subsequently classified as mild alcohol withdrawal syndrome (mild-AWS) patients (Cushman score ≤ 4, no benzodiazepine prescription, N = 17) or moderate alcohol withdrawal syndrome (moderate-AWS) patients (Cushman score > 4, benzodiazepine prescription, N = 37). Patients with severe withdrawal complications (delirium tremens or seizures) were not included. Mild-AWS patients presented similar grey matter volume and sleep quality as healthy controls, but lower processing speed and episodic memory performance. Compared to healthy controls, moderate-AWS patients presented non-rapid eye movement sleep alterations, widespread grey matter shrinkage and lower performance for all the cognitive domains assessed (processing speed, short-term memory, executive functions and episodic memory). Moderate-AWS patients presented a lower percentage of slow-wave sleep, grey matter atrophy in fronto-insular and thalamus/hypothalamus regions, and lower short-term memory and executive performance than mild-AWS patients. Mediation analyses revealed both direct and indirect (via fronto-insular and thalamus/hypothalamus atrophy) relationships between poor sleep quality and cognitive performance. Alcohol withdrawal syndrome severity, which reflects neurotoxic hyperglutamatergic activity, should be considered as a critical factor for the development of non-rapid eye movement sleep alterations, fronto-insular atrophy and executive impairments in recently detoxified alcohol use disorder patients. The glutamatergic activity is involved in sleep-wake circuits and may thus contribute to molecular mechanisms underlying alcohol-related brain damage, resulting in cognitive deficits. Alcohol withdrawal syndrome severity and sleep quality deserve special attention for a better understanding and treatment of brain and cognitive alterations observed early in abstinence, and ultimately for more efficient relapse prevention strategies.

The recognition and management of protracted alcohol withdrawal may improve and modulate the pharmacological treatment of alcohol use disorder

2020 ◽  
Vol 34 (11) ◽  
pp. 1171-1175
Author(s):  
Fabio Caputo ◽  
Mauro Cibin ◽  
Antonella Loche ◽  
Roberto De Giorgio ◽  
Giorgio Zoli
Keyword(s):  
Alcohol Use ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Alcohol Withdrawal Syndrome ◽  
Signs And Symptoms ◽  
Pharmacological Therapy ◽  
Acute Stage ◽  
Gamma Aminobutyric Acid ◽  
Alcohol Relapse ◽  
Time Frames

About 50% of persons with an alcohol use disorder may have symptoms of alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption. Protracted alcohol withdrawal (PAW), an underestimated and not yet clearly defined clinical condition that follows the acute stage of AWS, is characterized by the presence of substance-specific signs and symptoms (i.e. anxiety, irritability, mood instability, insomnia, craving) common to acute AWS, but persisting beyond the generally expected acute AWS time frames. Considering that PAW symptoms are mainly related to the neuro-adaptive changes of gamma-aminobutyric acid (GABA) and N-methyl-d-aspartate (NMDA) systems, naltrexone, nalmefene, and disulfiram may not be able to suppress the symptoms of PAW. After treatment of the acute phase of AWS, a more specifically pharmacological therapy able to suppress PAW symptoms could perhaps be used earlier and may be more helpful in preventing the risk of alcohol relapse, which remains higher during the first months of treatment. In light of this, medications acting on GABA and NMDA neurotransmitter systems to counterbalance the up-regulation of NMDA and the down-regulation of GABA could be employed in combination and started as soon as possible.

scholarly journals Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review

2020 ◽  
Vol 21 (17) ◽  
pp. 6413 ◽  
Author(s):  
Shao-Cheng Wang ◽  
Yuan-Chuan Chen ◽  
Shaw-Ji Chen ◽  
Chun-Hung Lee ◽  
Ching-Ming Cheng
Keyword(s):  
Liver Disease ◽  
Alcohol Use ◽  
Gut Microbiota ◽  
Alcoholic Hepatitis ◽  
Alcohol Use Disorder ◽  
Gene Editing ◽  
Intestinal Barrier ◽  
The United States ◽  
Alcohol Addiction ◽  
Life Years

Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut–brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.

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