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.

Alcohol withdrawal syndrome in ICU patients: Clinical features, management, and outcome predictors

Background Alcohol withdrawal syndrome (AWS) is a common condition in hospitalized patients, yet its epidemiology in the ICU remains poorly characterized. Methods Retrospective cohort of patients admitted to the Nantes University Hospital ICU between January 1, 2017, and December 31, 2019, and coded for AWS using ICD-10 criteria. The objective of the study was to identify factors associated with complicated hospital stay defined as ICU length of stay ≥7 days or hospital mortality. Results Among 5,641 patients admitted to the ICU during the study period, 246 (4.4%) were coded as having AWS. Among them, 42 had exclusion criteria and 204 were included in the study. The three main reasons for ICU admission were sepsis (29.9%), altered consciousness (29.4%), and seizures (24%). At ICU admission, median Cushman’s score was 6 [4–9] and median SOFA score was 3 [2–6]. Delirium tremens occurred in half the patients, seizures in one fifth and pneumonia in one third. Overall, 48% of patients developed complicated hospital stay, of whom 92.8% stayed in the ICU for ≥7 days, 36.7% received MV for ≥7 days, and 16.3% died during hospital stay. By multivariable analysis, two factors were associated with complicated hospital stay: a higher number of organ dysfunctions at ICU admission was associated with a higher risk of complicated hospital stay (OR, 1.18; 95CI, 1.05–1.32, P = 0.005), whereas ICU admission for seizures was associated with a lower risk of complicated hospital stay (OR, 0.14; 95%CI, 0.026–0.80; P = 0.026). Conclusions AWS in ICU patients chiefly affects young adults and is often associated with additional factors such as sepsis, trauma, or surgery. Half the patients experienced an extended ICU stay or death during the hospital stay. The likelihood of developing complicated hospital stay relied on the reason for ICU admission and the number of organ dysfunctions at ICU admission.

Quantitative Electroencephalographic Analysis of Delirium Tremens Development Following Alcohol-withdrawal Seizure

Seizures and delirium tremens (DTs) are recognized as severe alcohol-withdrawal symptoms. Prolonged admission and serious complications associated with alcohol-withdrawal are responsible for increased costs and use of medical and social resources. We compared differences in quantitative electroencephalography (EEG) in patients after alcohol-withdrawal seizures (AWS; n = 13), performed in the intensive care unit within 48 h of admission, and in age- and sex-matched healthy controls. We also investigated the prognostic value of quantitative EEG, for the development of alcohol DTs after AWS in a retrospective, case‒control study. The spectral power of each band frequency and the ratio of the theta to alpha band (TAR) in the electroencephalogram were analysed using iSyncBrain® (iMediSync, Inc., Korea). The beta frequency and the alpha frequency band power were significantly higher and lower, respectively, in patients than in age- and sex-matched healthy controls. In AWS patients with DTs, the relative beta3 power was lower, particularly in the left frontal area, and the TAR was significantly higher in the central channel than in those without DTs. Quantitative EEG showed neuronal excitability and decreased cognitive activities characteristic of AWS patients associated with alcohol withdrawal state and we demonstrated that quantitative EEG also might be a helpful tool for detecting patients at high risk of developing DTs during an alcohol-dependence period.