Advances in drug and alcohol research最新文献

{"title":"Epigenetic regulation of microglia and neurons by proinflammatory signaling following adolescent intermittent ethanol (AIE) exposure and in human AUD.","authors":"Fulton T Crews, Victoria Macht, Ryan P Vetreno","doi":"10.3389/adar.2024.12094","DOIUrl":"10.3389/adar.2024.12094","url":null,"abstract":"<p><p>Adolescent alcohol drinking is linked to high rates of adult alcohol problems and alcohol use disorder (AUD). The Neurobiology of Alcohol Drinking in Adulthood (NADIA) consortium adolescent intermittent ethanol (AIE) models adolescent binge drinking, followed by abstinent maturation to adulthood to determine the persistent AIE changes in neurobiology and behavior. AIE increases adult alcohol drinking and preference, increases anxiety and reward seeking, and disrupts sleep and cognition, all risks for AUD. In addition, AIE induces changes in neuroimmune gene expression in neurons and glia that alter neurocircuitry and behavior. HMGB1 is a unique neuroimmune signal released from neurons and glia by ethanol that activates multiple proinflammatory receptors, including Toll-like receptors (TLRs), that spread proinflammatory gene induction. HMGB1 expression is increased by AIE in rat brain and in post-mortem human AUD brain, where it correlates with lifetime alcohol consumption. HMGB1 activation of TLR increase TLR expression. Human AUD brain and rat brain following AIE show increases in multiple TLRs. Brain regional differences in neurotransmitters and cell types impact ethanol responses and neuroimmune gene induction. Microglia are monocyte-like cells that provide trophic and synaptic functions, that ethanol proinflammatory signals sensitize or \"prime\" during repeated drinking cycles, impacting neurocircuitry. Neurocircuits are differently impacted dependent upon neuronal-glial signaling. Acetylcholine is an anti-inflammatory neurotransmitter. AIE increases HMGB1-TLR4 signaling in forebrain, reducing cholinergic neurons by silencing multiple cholinergic defining genes through upregulation of RE-1 silencing factor (REST), a transcription inhibitor known to regulate neuronal differentiation. HMGB1 REST induction reduces cholinergic neurons in basal forebrain and cholinergic innervation of hippocampus. Adult brain hippocampal neurogenesis is regulated by a neurogenic niche formed from multiple cells. <i>In vivo</i> AIE and <i>in vitro</i> studies find ethanol increases HMGB1-TLR4 signaling and other proinflammatory signaling as well as reducing trophic factors, NGF, and BDNF, coincident with loss of the cholinergic synapse marker vChAT. These changes in gene expression-transcriptomes result in reduced adult neurogenesis. Excitingly, HMGB1 antagonists, anti-inflammatories, and epigenetic modifiers like histone deacetylase inhibitors restore trophic the neurogenesis. These findings suggest anti-inflammatory and epigenetic drugs should be considered for AUD therapy and may provide long-lasting reversal of psychopathology.</p>","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"4 ","pages":"12094"},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Substance abuse and the microbiome","authors":"P. Nagarkatti, M. Nagarkatti, Shilpa Buch","doi":"10.3389/adar.2024.12734","DOIUrl":"https://doi.org/10.3389/adar.2024.12734","url":null,"abstract":"","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"45 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140077719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol use and the pain system","authors":"M. Vigorito, Sulie L. Chang","doi":"10.3389/adar.2024.12005","DOIUrl":"https://doi.org/10.3389/adar.2024.12005","url":null,"abstract":"The World Health Organization’s epidemiological data from 2016 revealed that while 57% of the global population aged 15 years or older had abstained from drinking alcohol in the previous year, more than half of the population in the Americas, Europe, and Western Pacific consumed alcohol. The spectrum of alcohol use behavior is broad: low-risk use (sensible and in moderation), at-risk use (e.g., binge drinking), harmful use (misuse) and dependence (alcoholism; addiction; alcohol use disorder). The at-risk use and misuse of alcohol is associated with the transition to dependence, as well as many damaging health outcomes and preventable causes of premature death. Recent conceptualizations of alcohol dependence posit that the subjective experience of pain may be a significant contributing factor in the transition across the spectrum of alcohol use behavior. This narrative review summarizes the effects of alcohol at all levels of the pain system. The pain system includes nociceptors as sensory indicators of potentially dangerous stimuli and tissue damage (nociception), spinal circuits mediating defensive reflexes, and most importantly, the supraspinal circuits mediating nocifensive behaviors and the perception of pain. Although the functional importance of pain is to protect from injury and further or future damage, chronic pain may emerge despite the recovery from, and absence of, biological damage (i.e., in the absence of nociception). Like other biological perceptual systems, pain is a construction contingent on sensory information and a history of individual experiences (i.e., learning and memory). Neuroadaptations and brain plasticity underlying learning and memory and other basic physiological functions can also result in pathological conditions such as chronic pain and addiction. Moreover, the negative affective/emotional aspect of pain perception provides embodied and motivational components that may play a substantial role in the transition from alcohol use to dependence.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"44 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139599618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent alcohol drinking interaction with the gut microbiome: implications for adult alcohol use disorder","authors":"Bruk Getachew, S. Hauser, Samia Bennani, Nacer El Kouhen, Youssef Sari, Yousef Tizabi","doi":"10.3389/adar.2024.11881","DOIUrl":"https://doi.org/10.3389/adar.2024.11881","url":null,"abstract":"Reciprocal communication between the gut microbiota and the brain, commonly referred to as the “gut-brain-axis” is crucial in maintaining overall physiological homeostasis. Gut microbiota development and brain maturation (neuronal connectivity and plasticity) appear to be synchronized and to follow the same timeline during childhood (immature), adolescence (expansion) and adulthood (completion). It is important to note that the mesolimbic reward circuitry develops early on, whereas the maturation of the inhibitory frontal cortical neurons is delayed. This imbalance can lead to increased acquirement of reward-seeking and risk-taking behaviors during adolescence, and consequently eventuate in heightened risk for substance abuse. Thus, there is high initiation of alcohol drinking in early adolescence that significantly increases the risk of alcohol use disorder (AUD) in adulthood. The underlying causes for heightened AUD risk are not well understood. It is suggested that alcohol-associated gut microbiota impairment during adolescence plays a key role in AUD neurodevelopment in adulthood. Furthermore, alcohol-induced dysregulation of microglia, either directly or indirectly through interaction with gut microbiota, may be a critical neuroinflammatory pathway leading to neurodevelopmental impairments and AUD. In this review article, we highlight the influence of adolescent alcohol drinking on gut microbiota, gut-brain axis and microglia, and eventual manifestation of AUD. Furthermore, novel therapeutic interventions via gut microbiota manipulations are discussed briefly.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":" 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139621128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of pharmacotherapies for diabetes on nicotine, food, and water intake in insulin-resistant rats","authors":"Sebastian Ortegon, Priscilla Giner, Bryan Cruz, Luis M. Carcoba, Benjamin Clapp, Deborah J. Clegg, Laura E. O’Dell","doi":"10.3389/adar.2023.11812","DOIUrl":"https://doi.org/10.3389/adar.2023.11812","url":null,"abstract":"The intersectionality between diabetes medications and nicotine consumption was assessed in female and male rats. Briefly, the rats were fed a high-fat diet (HFD) or regular diet (RD) for 4 weeks. Then separate groups received vehicle or a low dose of streptozotocin (STZ; 25 mg/kg). Three days later, insulin resistance was assessed by measuring plasma glucose levels for 180 min following an injection of insulin (0.75 U/kg). The rats were then prepared with jugular catheters, and they were given 23 h access to nicotine intravenous self-administration (IVSA) in 4 days cycles with 3 days of forced abstinence in their home cages where they consumed their respective diet. During the IVSA sessions, operant responses for food and water and changes in body weight were recorded. Prior to administration of the pharmacotherapies, the rats were given access to two doses of nicotine (0.015 then 0.03 mg/kg for the remainder of the study). Then, daily injections of the pharmacotherapies were given at the onset of dark cycle (6 p.m.) in the following order: 1) dapagliflozin (3.0 then 10.0 mg/kg), 2) insulin (0.75 U/kg twice), and 3) bromocriptine (3.0 then 10.0 mg/kg). The results suggest that our HFD+STZ regiment induced insulin resistance in female and male rats. Also, the HFD-fed rats displayed higher nicotine intake than RD controls, regardless of sex. Administration of insulin, but not dapagliflozin or bromocriptine, normalized nicotine intake in HFD-fed rats to control levels. These results have clinical implications regarding the potential efficacy of insulin to control excessive nicotine intake in persons with diabetes.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"24 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139450769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multicomponent ethanol response battery across a cumulative dose ethanol challenge reveals diminished adolescent rat ethanol responsivity relative to adults","authors":"R. Vetreno, Jeffrey Campbell, F. Crews","doi":"10.3389/adar.2023.11888","DOIUrl":"https://doi.org/10.3389/adar.2023.11888","url":null,"abstract":"Adolescence is a conserved developmental period associated with low alcohol responsivity, which can contribute to heavy drinking and development of an alcohol use disorder (AUD) later in life. To investigate ethanol responsivity between adolescent and adult rats, we developed an ethanol response battery (ERB) to assess acute ethanol responses across cumulative doses of ethanol during the rising phase of the blood ethanol curve. We tested the hypothesis that adolescent male and female rats would exhibit lower ethanol responsivity to a cumulative ethanol challenge relative to adults. Male and female adolescent (postnatal day [P]40) and adult (P85) Wistar rats underwent ERB assessment following consecutive doses of ethanol (i.e., 1.0, 1.0, and 1.0 g/kg) to produce cumulative ethanol doses of 0.0, 1.0, 2.0, and 3.0 g/kg. The ERB consisted of (1) the 6-point behavioral intoxication rating scale, (2) body temperature assessment, (3) tail blood collection, (4) accelerating rotarod assessment, (5) tilting plane assessment, and (6) loss of righting reflex (LORR) assessment. Across cumulative ethanol doses, adolescent and adult rats evidenced progressive changes in ERB measures. On the ERB, adolescent rats of both sexes evidenced (1) lower intoxication rating, (2) blunted hypothermic responses, particularly in females, (3) longer latencies to fall from the accelerating rotarod, and (4) less tilting plane impairment relative to adults despite comparable BECs. All adult rats, regardless of sex, displayed a LORR at the 3.0 g/kg cumulative ethanol dose while among the adolescent rats, only one male rat and no females showed the LORR. These data reveal decreased adolescent ethanol responsivity across body temperature, intoxication, balance, and coordination responses to a cumulative ethanol challenge as assessed using the novel ERB relative to adults. The results of this study suggest that adolescent-specific low ethanol responsivity may contribute to adolescent binge drinking and increased risk for development of an AUD.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"43 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138950892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol induced behavioral and immune perturbations are attenuated by activation of CB2 cannabinoid receptors","authors":"Aaliyah Roberts, Mahli Christian, Lizbeth Nivar Dilone, Natania Nelson, Mark Joseph Endrino, A. Kneebone, Shymaa Embaby, Justin Fernandez, Qing-Rong Liu, E. Onaivi, Berhanu Geresu Kibret","doi":"10.3389/adar.2023.11602","DOIUrl":"https://doi.org/10.3389/adar.2023.11602","url":null,"abstract":"The endocannabinoidome (eCBome) is the expanded endocannabinoid system (ECS) and studies show that there is a link between this system and how it modulates alcohol induced neuroinflammation. Using conditional knockout (cKO) mice with selective deletion of cannabinoid type 2 receptors (CB2Rs) in dopamine neurons (DAT-Cnr2) and in microglia (Cx3Cr1-Cnr2), we investigated how CB2Rs modulate behavioral and neuroinflammation induced by alcohol. Behavioral tests including locomotor and wheel running activity, rotarod performance test, and alcohol preference tests were used to evaluate behavioral changes induced by alcohol. Using ELISA assay, we investigated the level of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1α (IL-1α), and interleukin-1β (IL-1β) in the hippocampus of mice. The findings demonstrated that locomotor activity, wheel running, and rotarod performance activities were significantly affected by cell-type specific deletion of CB2Rs in dopamine neurons and microglia. The non-selective CB2R agonist, WIN 55,212-2, reduced alcohol preference in the wild type and cell-type specific CB2R cKO mice. In addition, the result showed that cell-type specific deletion of CB2Rs per se and administration of alcohol to CB2R cKO mice increased the expression of proinflammatory cytokines in the hippocampus. These findings suggest the involvement of CB2Rs in modulating behavioral and immune alterations induced by alcohol.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":" 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138963168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging mechanisms by which endocannabinoids and their derivatives modulate bacterial populations within the gut microbiome","authors":"M. Ellermann","doi":"10.3389/adar.2023.11359","DOIUrl":"https://doi.org/10.3389/adar.2023.11359","url":null,"abstract":"Bioactive lipids such as endocannabinoids serve as important modulators of host health and disease through their effects on various host functions including central metabolism, gut physiology, and immunity. Furthermore, changes to the gut microbiome caused by external factors such as diet or by disease development have been associated with altered endocannabinoid tone and disease outcomes. These observations suggest the existence of reciprocal relationships between host lipid signaling networks and bacterial populations that reside within the gut. Indeed, endocannabinoids and their congeners such as N-acylethanolamides have been recently shown to alter bacterial growth, functions, physiology, and behaviors, therefore introducing putative mechanisms by which these bioactive lipids directly modulate the gut microbiome. Moreover, these potential interactions add another layer of complexity to the regulation of host health and disease pathogenesis that may be mediated by endocannabinoids and their derivatives. This mini review will summarize recent literature that exemplifies how N-acylethanolamides and monoacylglycerols including endocannabinoids can impact bacterial populations in vitro and within the gut microbiome. We also highlight exciting preclinical studies that have engineered gut bacteria to synthesize host N-acylethanolamides or their precursors as potential strategies to treat diseases that are in part driven by aberrant lipid signaling, including obesity and inflammatory bowel diseases.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"53 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138587962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent alcohol and nicotine exposure alters the adult response to alcohol use","authors":"S. Hauser, R. A. Waeiss, G. Deehan, E. Engleman, Richard L. Bell, Z. Rodd","doi":"10.3389/adar.2023.11880","DOIUrl":"https://doi.org/10.3389/adar.2023.11880","url":null,"abstract":"Adolescence through young adulthood is a unique period of neuronal development and maturation. Numerous agents can alter this process, resulting in long-term neurological and biological consequences. In the clinical literature, it is frequently reported that adolescent alcohol consumption increases the propensity to develop addictions, including alcohol use disorder (AUD), during adulthood. A general limitation of both clinical and human pre-clinical adolescent alcohol research is the high rate of co-using/abusing more than one drug during adolescence, such as co-using/abusing alcohol with nicotine. A primary goal of basic research is elucidating neuroadaptations produced by adolescent alcohol exposure/consumption that promote alcohol and other drug self-administration in adulthood. The long-term goal is to develop pharmacotherapeutics for the prevention or amelioration of these neuroadaptations. This review will focus on studies that have examined the effects of adolescent alcohol and nicotine exposure on adult alcohol consumption, the hypersensitivity of the mesolimbic dopaminergic system, and enhanced responses not only to alcohol but also to nicotine during adulthood. Again, the long-term goal is to identify potential cholinergic agents to prevent or ameliorate the consequences of, peri-adolescent alcohol abuse.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139247349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with perinatal substance use among Ethiopian women: an institutional-based cross-sectional study","authors":"J. Seid, Emam Mohammed, Y. Muktar","doi":"10.3389/adar.2023.11913","DOIUrl":"https://doi.org/10.3389/adar.2023.11913","url":null,"abstract":"Introduction: Substance use during the perinatal period is a significant public health concern, as it can have potential adverse effects on maternal and neonatal health outcomes. Unexpectedly, no previous studies have been conducted to assess the prevalence of substance use during the perinatal period among Ethiopian women. Therefore, this study aimed to determine the magnitude of substance use and its determinant factors during the perinatal period.Method: We conducted a hospital-based descriptive cross-sectional study among a systematically selected sample of 418 women who attended perinatal care between May and July 2022. Data were collected using an interviewer-administered structured questionnaire. Multivariate logistic regression analysis, with a 95% confidence interval and p-values less than 0.05, was employed to identify factors associated with substance use behavior.Result: The prevalence of perinatal substance use was found to be 38.3% (95% CI: 33.5–43.5). Of the women who used substances, 109 (26.1%) reported using chat, 46 (11.0%) reported alcohol consumption, and 5 (1.20%) reported using shisha. Factors significantly associated with substance use behavior during the perinatal period included a history of obstetric complications (AOR = 1.722, 95% CI: 1.022–2.902), the presence of chronic medical conditions (AOR = 3.784, 95% CI: 2.164–6.615), experiencing physical abuse (AOR = 5.323, 95% CI: 2.171–13.050), depression (AOR = 1.963, 95% CI: 1.028–3.749), and experiencing sleep disturbances (AOR = 2.016, 95% CI: 0.975–4.168). Conversely, giving birth to a live baby was found to be a protective factor against substance use behavior (AOR = 0.389, 95% CI: 0.187–0.810).Discussion: This study highlights a high prevalence of substance abuse among women during the perinatal period. In light of these findings, a comprehensive approach is recommended to address perinatal substance use among Ethiopian women. This should include the integration of preventive educational programs into perinatal care.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"16 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139275866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}