Addiction Biology最新文献

The consumption of alcohol affects 400 million people worldwide, where it is responsible for 7% of deaths. Treatment success rates in this field remain limited. Only 15% of those who need treatment get it. Despite treatment, alcohol intake reoccurs in up to 90% of the cases. The use of disulfiram in preventing alcohol reoccurrence is attributed to its unique mechanism of action as an aversive agent, which causes the patient to experience unpleasant physical symptoms when they consume alcohol. The objective of this study is to confirm and illustrate the efficacy of disulfiram in combination with non-pharmacological intervention for persons with severe AUD. Clinical data from 45 patients of an outpatient treatment programme, including the application of disulfiram (2011–2023) were analysed to assess abstinence rates, craving impact, and demographic factors. Moreover, our analyses aimed to identify predictors and moderators of continuous abstinence duration. The study cohort comprised patients with severe AUD and high rates of comorbidities, the majority of which were affective disorders. During treatment, 50% of patients remained abstinent for at least 1 year. No significant differences were identified in craving, sex or comorbidities compared with those who experienced a return to substance use after treatment initiation. Disulfiram underlined its efficacy and tolerability as an adjunct to addiction-focused treatment in a typical clinical cohort of patients severely affected by AUD. Moreover, our analyses align with previous research indicating that disulfiram appears to allow patients with AUD to resist craving episodes, therefore avoiding impulsive reoccurrences of alcohol intake.

Short-video addiction (SVA) has become a growing concern among adolescents. Bullying victimization (BV) is considered a significant factor contributing to it, yet its relationship with SVA remains underexplored. This study investigated the role of BV in SVA, examining developmental and psychological pathways across middle school students (MSS; n = 1269), college students (CS; n = 1615) and a replicated college sample (RCS; n = 112). Descriptive statistics revealed significant correlations between SVA and BV, including subdimensions such as verbal, physical and relational bullying, as well as negative affect (NA). Mediation analyses showed that NA partially mediated the relationship between BV and SVA across both MSS and CS groups, although mediation effects were absent in addicted subgroups, highlighting differing psychological pathways between addicted and nonaddicted populations. Neuroimaging analyses in the RCS sample identified spontaneous functional brain activity linked to SVA in the inferior temporal gyrus (ITG) and parahippocampal gyrus (PHG), with intersubject representational similarity analyses (IS-RSA) further associating PHG and dorsomedial prefrontal cortex (DMPFC) activity patterns with intersubject variations in SVA. These findings underscore bullying victimization as a critical predictor of short video addiction, mediated by NA in nonaddicted groups, and illuminate spontaneous brain activity patterns associated with addiction.

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are characterized with heightened negative emotionality (NE) and are frequently comorbid. However, little research has investigated NE in individuals with comorbid AUD/PTSD. We compared psychological and biological markers of NE phenotypes, and alcohol-related outcomes between individuals with AUD with and without PTSD, and healthy controls. Additionally, we evaluated whether childhood trauma severity moderated these relationships. Participants [N = 1292; healthy controls (HC): n = 502 (38.9%); AUD only: n = 610 (47.2%), and AUD/PTSD (CMB); n = 180 (13.9%)] enrolled in the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol underwent clinical, biological and behavioural phenotyping that included psychiatric diagnoses, markers of negative emotionality and allostatic load, alcohol use behaviour, and history of childhood trauma. The CMB group had the most severe alcohol use and childhood trauma history. Psychological NE were the most dysregulated among the CMB group. Biological markers of NE were also dysregulated among the AUD and CMB group, where they displayed greater resting heart rate, diastolic blood pressure and HDL cholesterol relative to HC. Greater childhood trauma severity was associated with greater psychological NE. However, the childhood trauma did not moderate any relationship between diagnosis and NE phenotypes. These results highlight important differences in NE, childhood trauma and alcohol use in individuals with AUD with and without comorbid PTSD. Targeting NE and alcohol-related behaviours is critical in effective treatment of individuals with comorbid AUD/PTSD.

Trial Registration: ClinicalTrials.gov: NCT02231840.

Methamphetamine (METH) use leads to addiction, neurotoxicity, and neuroinflammation. Ibudilast, a toll-like receptor 4 (TLR4) inhibitor, has been shown to reduce METH-induced neuroinflammation and self-administration, but its specific role in neuronal TLR4 signalling and associated behavioural outcomes remains poorly understood. This study examined Ibudilast's effects on METH reward, drug-seeking behaviour, and TLR4 signalling in a rat self-administration model. Ibudilast was found to dose-dependently reduce METH intake and motivation for the drug, as evidenced by a downward shift in the dose–response curve and a decrease in breakpoint. Additionally, Ibudilast suppressed both cue- and METH priming-induced drug-seeking behaviours. Western blot analysis revealed elevated TLR4, p-NF-κB and IL-6 in the prefrontal cortex after 14 days of METH self-administration. These increases were significantly attenuated by Ibudilast treatment. Furthermore, local administration of Ibudilast in the prefrontal cortex led to a reduction in METH intake and motivation, as well as decreased TLR4 expression in this brain region. Immunofluorescence staining was revealed that TLR4 was expressed predominantly in neurons and microglia, with METH-induced upregulation of neuronal TLR4 being linked to apoptosis. Ibudilast restored normal spatial interactions between neurons and microglia, thereby mitigating neuroinflammation and neuronal damage. Furthermore, local injection of Ibudilast in the prefrontal cortex led to a reduction in METH intake and motivation, as well as decreased expression of TLR4 in the brain region. These findings underscore the critical role of neuronal TLR4 in METH addiction and highlight Ibudilast's therapeutic potential in addressing METH-related neuroinflammation and behavioural dysregulation.

The microbiota–gut–brain axis has been implicated in the pathology of substance use disorders (SUDs). In light of the brain's capability to reorganize itself in response to intrinsic and extrinsic stimuli, opioid-induced dysbiosis is likely to contribute to addictive behaviour through modulating neuroplasticity. In this study, a faecal microbiota transplantation (FMT) from a saline-donor was performed on morphine-treated rats to evaluate the effects of gut microbiota on morphine-induced metaplasticity and addictive behaviours. Male Wistar rats were treated with subcutaneous injections of 10 mg/kg morphine sulphate every 12 h for 9 days in an effort to induce dependence. The withdrawal syndrome was precipitated by injecting naloxone (1.5 mg/kg, ip) after the final dose of morphine. The tolerance was induced by repeated morphine injections over a period of 7 days (10 mg/kg, once a day, ip). FMT was applied daily through gavage of processed faeces 1 week before and during the morphine treatment. Field potential recordings (i.e., fEPSP) were carried out to assess short-term and long-term synaptic plasticity in the CA1 area of the hippocampus following Schaffer-collateral stimulation. Animals subjected to FMT exhibited significant reductions in naloxone-precipitated withdrawal syndrome (one-way ANOVA, p < 0.05). Tolerance to the analgesic effects of morphine was not affected by FMT (two-way ANOVA, p > 0.05). Following high-frequency stimulation (HFS) to induce long-term potentiation (LTP), a greater fEPSP slope was observed in morphine-treated animals (unpaired t test, p < 0.05). FMT from saline-donor rats diminished morphine-induced augmented LTP (unpaired t test, p < 0.05). These results highlighted the alleviating effects of FMT from saline-donors on morphine-induced metaplasticity and dependence potentially by modulating the dysbiosis of gut microbiota.

The reproducibility crisis in psychology has caused various fields to consider the reliability of their own findings. Many of the unfortunate aspects of research design that undermine reproducibility also threaten translation potential. In preclinical addiction research, the rates of translation have been disappointing. We tallied indices of transparency and accurate and thorough reporting in animal models of opioid addiction from 2019 to 2023. By examining the prevalence of these practices, we aimed to understand whether efforts to improve reproducibility are relevant to this field. For 255 articles, we report the prevalence of transparency measures such as preregistration, registered reports, open data and open code, as well as compliance to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. We also report rates of bias minimization practices (randomization, masking and data exclusion), sample size calculations and multiple corrections adjustments. Lastly, we estimated the accuracy of test statistic reporting using a version of StatCheck. All the transparency measures and the ARRIVE guideline items had low prevalence, including no cases of study preregistration and no cases where authors shared their analysis code. Similarly, the levels of bias minimization practices and sample size calculations were unsatisfactory. In contrast, adjustments for multiple comparisons were implemented in most articles (76.5%). Lastly, p-value inconsistencies with test statistics were detected in about half of papers, and 11% contained statistical significance errors. We recommend that researchers, journal editors and others take steps to improve study reporting and to facilitate both replication and translation.

With the many negative health consequences of cigarette smoking, quitting is known to improve health in multiple domains. Using positron emission tomography/computed tomography (PET/CT) scanning, our group previously demonstrated that smokers have lower levels than nonsmokers of translocator protein binding both acutely and following overnight abstinence. Here, we sought to determine the effects of longer smoking abstinence on this marker of gliosis for microglia and astroglia, as well as explore associations between the marker and smoking-related symptoms. This observational study was performed in an academic VA medical centre. Fifty-nine generally healthy Veterans who were either nonsmokers (n = 15) or smokers (n = 44) participated in the study. Participants completed an intake visit to evaluate for inclusion/exclusion criteria, [¹⁸F]FEPPA PET/CT scanning and a structural magnetic resonance imaging scan. Smokers were alternately assigned either to smoke to satiety (n = 24) before scanning or undergo three nights of continuous abstinence prior to scanning using contingency management (n = 20 completed this protocol and scanning). The smoker satiety group had a significantly lower mean whole brain (WB) standardized uptake value (SUV) for [¹⁸F]FEPPA binding than both the nonsmoking (−15.3%) and abstinent smoker (−12.3%) groups. The nonsmoking control and abstinent smoker groups had mean WB SUVs that were not significantly different from one another (3.0% group difference). In an exploratory analysis, a significant inverse relationship was found between WB SUVs and mood ratings for smokers, indicating that higher levels of TSPO binding were associated with worse mood. The central findings here support previous studies demonstrating lower levels of the marker for gliosis in satiated smokers and imply normalization with elimination of cigarette smoke constituents from the body, although other explanations for study results (e.g., alterations in radioligand delivery or clearance of radioligand by cigarette smoke constituents) are possible. These findings may represent a previously unknown health benefit of quitting smoking.

Opioid use disorder (OUD) is a significant mental health problem, with prolonged usage potentially resulting in tolerance, addiction and cognitive decline, including learning and memory deficiency. At present, pharmacotherapy serves as the primary treatment approach for OUD. However, despite its status as a cornerstone of treatment, pharmacotherapy has certain limitations, thereby mandating the exploration of alternative modalities. This study evaluated the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) in multiple cognitive domains in morphine-withdrawn rats. To induce morphine dependence, the rats were administered 10 mg/kg morphine for 10 consecutive days. taVNS was administered to the left ear of each rat and continued for 2 weeks. After electrical stimulation, various cognitive and emotional functions were assessed through related behavioural tasks, including open field, Y-maze, novel object recognition and elevated plus maze tests. GFAP, Iba1 and BDNF expression levels in the hippocampus were determined via quantitative polymerase chain reaction (qPCR). Our investigation revealed that taVNS ameliorated the impairment of working and recognition memory induced by morphine in behavioural tests. Additionally, it exerts an anxiolytic effect. Moreover, taVNS counteracted the decreased concentration of brain-derived neurotrophic factor (BDNF) and elevated levels of glial fibrillary acidic protein (GFAP) caused by morphine. Nonetheless, taVNS applied only at a frequency of 100 Hz has the potential to lower Iba1 levels independently of prior exposure to morphine. taVNS has been shown to exert a neuroprotective effect on morphine-withdrawn rats. This outcome indicates that taVNS can be employed as a supplementary therapy with other pharmacological interventions for OUD.

Background. Alcohol use disorder (AUD) is prevalent during young adulthood, and this risk may be linked to aberrations in neurodevelopmental processes. Prior studies examining white matter (WM) integrity in young adult individuals with AUD have shown considerable variability. This is due in part because traditional tensor related metrics such as fractional anisotropy are subject to limitations in estimation precision at sites of crossing or curving fibres. In response, to better understand differences in WM integrity of young adults with AUD, this study sought to uniquely employ two WM integrity measurement domains. Methods. Twenty-five participants (n = 14 female) diagnosed with AUD and 33 social drinkers (n = 19 female) underwent structural and diffusion-weighted imaging. Diffusion-weighted images were processed to extract diffusion tensor (DTI) and neurite orientation dispersion and density (NODDI) metrics in major WM tracts for comparison between the two groups. Results. We identified decreased axial diffusivity in portions of frontolimbic and corticostriatal WM tracts, and increased orientation dispersion at overlapping tracts in participants with AUD relative to social drinkers. Conclusions. These results may represent early-stage neural immune system activation and axonal reorganization targeting frontolimbic and corticostriatal WM tracts, therein associated with behaviours linked to AUD. This is the first study combining DTI and NODDI metrics to identify early-stage indicators of alcohol-related neurobiological pathology in young adults with AUD compared to social drinkers.

Nonneuronal cells mediate neurotransmission and drug addiction. However, the role of oligodendrocytes in stress-induced cocaine relapses remains unclear. In the present study, we investigated the role of the oligodendrocyte-abundant molecule crystallin alpha B (CRYAB) in cocaine-induced conditioned place preference (CPP) relapsed by restraint stress. RNA sequencing (RNA-seq) was performed to identify oligodendrocytes and stress-associated molecules in the nucleus accumbens (NAcc) of both drug users and cocaine-treated animals. Further, we studied which cell subtypes in the brain express CRYAB. The effects of stress hormones and cocaine on CRYAB expression were evaluated in vitro in human oligodendrocytes. CRYAB is upregulated in the NAcc of both cocaine-treated animals and drug users. CRYAB levels in the NAcc of mice increased during CPP development but decreased following stress-induced relapse. Interestingly, CRYAB is expressed in oligodendrocytes in the NAcc of mice. Extracellular CRYAB levels are regulated by cocaine and stress hormone treatments in oligodendrocyte cultures. Dopamine levels in the NAcc and CPP development of CPP are significantly increased by cocaine in CRYAB knockout (KO) mice. Further, we demonstrated that CRYAB binds to the excitatory amino acid transporter 2 (EAAT2) in the NAcc of mice treated with cocaine. We suggest that oligodendrocyte-derived CRYAB regulates dopamine neurotransmission and stress-evoked cocaine reward behaviour via the modulation of EAAT2 in the NAcc.