Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction.

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD.

Isolated during adolescence: long-term impact on social behavior, pain sensitivity, and the oxytocin system in male and female rats.

Background: Adolescent social isolation (ASI) has profound long-term effects on behavioral and neural development. Despite this, the specific long-term impact of ASI during different adolescent stages and across sexes remain underexplored.

Methods: Our study addresses this gap by examining the effects of early- and late- adolescent social isolation on both male and female rats.

Alcohol Use Disorder-Associated DNA Methylation in the Nucleus Accumbens and Dorsolateral Prefrontal Cortex.

Background: Alcohol use disorder (AUD) has a profound public health impact. However, understanding of the molecular mechanisms that underlie the development and progression of AUD remains limited. Here, we investigated AUD-associated DNA methylation changes within and across 2 addiction-relevant brain regions, the nucleus accumbens and dorsolateral prefrontal cortex.

A systematic review and meta-analysis on the transcriptomic signatures in alcohol use disorder.

Currently available clinical treatments on alcohol use disorder (AUD) exhibit limited efficacy and new druggable targets are required. One promising approach to discover new molecular treatment targets involves the transcriptomic profiling of brain regions within the addiction neurocircuitry, utilizing animal models and postmortem brain tissue from deceased patients with AUD. Unfortunately, such studies suffer from large heterogeneity and small sample sizes.

Psilocybin administered following extinction sessions does not affect subsequent cocaine cue reinstatement in male and female rats and mice.

There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects.

Polygenic risk scores for nicotine use and family history of smoking are associated with smoking behaviour.

Introduction: Formal genetics studies show that smoking is influenced by genetic factors; exploring this on the molecular level can offer deeper insight into the etiology of smoking behaviours.

Methods: Summary statistics from the latest wave of the GWAS and Sequencing Consortium of Alcohol and Nicotine (GSCAN) were used to calculate polygenic risk scores (PRS) in a sample of ~2200 individuals who smoke/individuals who never smoked. The associations of smoking status with PRS for Smoking Initiation (i.

Cell type-specific Multi-Omics Analysis of Cocaine Use Disorder in the Human Caudate Nucleus.

Structural and functional alterations in the brain's reward circuitry are present in cocaine use disorder (CocUD), but their molecular underpinnings remain unclear. To investigate these mechanisms, we performed single-nuclei multiome profiling on postmortem caudate nucleus tissue from six individuals with CocUD and eight controls. We profiled 31,178 nuclei, identifying 13 cell types including D1- and D2-medium spiny neurons (MSNs) and glial cells.

Good Practice Guideline for Preclinical Alcohol Research: The STRINGENCY Framework.

Research in the field of preclinical alcohol research, but also science in general, has a problem: Many published scientific results cannot be repeated. As a result, findings from preclinical research often do not translate well to humans, causing increasing disappointment and calls for restructuring of preclinical research, that is, better reproducibility of preclinical research. However, the replication crisis is an inherent problem in biomedical research.

Conditional deletion of the AMPA-GluA1 and NMDA-GluN1 receptor subunit genes in midbrain D1 neurons does not alter cocaine reward in mice.

Synaptic plasticity in the mesolimbic dopamine (DA) system contributes to the neural adaptations underlying addictive behaviors and relapse. However, the specific behavioral relevance of glutamatergic excitatory drive onto dopamine D1 receptor (D1R)-expressing neurons in mediating the reinforcing effect of cocaine remains unclear. Here, we investigated how midbrain AMPAR and NMDAR function modulate cocaine reward-related behavior using mutant mouse lines lacking the glutamate receptor genes Gria1 or Grin1 in D1R-expressing neurons (GluA1 or GluN1, respectively).

The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions.

Substitution therapy for patients with alcohol dependence: Mechanisms of action and efficacy.

New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options for opioid and nicotine use disorders. So far, there has been little attention to substitution therapy for the treatment of AD.

Associations of Menstrual Cycle and Progesterone-to-Estradiol Ratio With Alcohol Consumption in Alcohol Use Disorder: A Sex-Separated Multicenter Longitudinal Study.

Objective: Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD.

Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats.

Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin's general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development.

Psilocybin does not induce the vulnerability marker HSP70 in neurons susceptible to Olney's lesions.

S-ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, and psilocybin, a 5-hydroxy-tryptamine (serotonin) 2A receptor (5-HTR) agonist, are reported as effective rapid-acting antidepressants. Both compounds increase glutamate signalling and evoke cortical hyperexcitation. S-ketamine induces neurotoxicity especially in the retrosplenial cortex (Olney's lesions).

Sex- and age-specific effects on the development of addiction and compulsive-like drinking in rats.

Background: Biological factors are known to influence disease trajectories and treatment effectiveness in alcohol addiction and preclinical and clinical evidence suggests that sex is an important factor influencing disease dynamics in alcohol dependence. Another critical factor is age at first intoxicating drink, which has been identified as a risk factor for later alcohol binging. Preclinical research allows prospective monitoring of rodents throughout the lifespan, providing very detailed information that cannot be acquired in humans.

Chronic alcohol consumption and COVID-19 infection risk: A narrative review.

During the COVID-19 pandemic, many potential risk groups have been identified, such as those with obesity, diabetes, preexisting organ injuries, and several other conditions. Smoking is the most reported substance use disorder linked to increased COVID-19 hospitalization rate and disease severity. In relation to smoking, we discuss the impairment of the innate and the adaptive immune systems as being among the main potential reasons for increased COVID-19 infection risk and severity.

Chronic alcohol intake regulates expression of SARS-CoV2 infection-relevant genes in an organ-specific manner.

Background: Chronic alcohol consumption and alcohol use disorder have a tremendous impact on the patient's psychological and physiological health. There is evidence that chronic alcohol consumption influences SARS-CoV2 infection risk, but so far, the molecular mechanism underlying such an effect is unknown.

Methods: We generated the expression data of SARS-CoV2 infection-relevant genes (Ace2, Tmprss2, and Mas) in different organs in rat models of chronic alcohol exposure and alcohol dependence.

Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

Aims: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population).