Advances in drug and alcohol research最新文献

{"title":"Methadone alters the peripheral inflammatory and central immune landscape following prenatal exposure in rats.","authors":"Nethra K Madurai, Yuma Kitase, Sarah Hamimi, Shannon E Kirk, Riley Sevensky, Sindhu Ramachandra, Sankar Muthukumar, Vikram Vasan, Maide Ozen, Gwendolyn Gerner, Shenandoah Robinson, Lauren L Jantzie","doi":"10.3389/adar.2022.10792","DOIUrl":"10.3389/adar.2022.10792","url":null,"abstract":"<p><p>Opioid use during pregnancy continues to rise at alarming rates with a parallel trend in the number of infants and children exposed to opioid medications each year. Prenatal opioid exposure (POE) occurs at a critical timepoint in neurodevelopment disrupting intricate pathways essential for neural-immune maturation with the potential for devastating long-term consequences. Understanding the mechanisms underlying injury associated with POE is essential to address long-term outcomes and identify diagnostic and therapeutic biomarkers in this vulnerable patient population. Using an established preclinical model of POE, we investigated changes in cerebral and peripheral inflammation and peripheral blood mononuclear cell (PBMC) activity. We hypothesized that neuroinflammation, as defined by changes in specific cerebral immune cell populations, would exist in adult rats following POE concomitant with sustained peripheral immune hyperreactivity (SPIHR). Our data demonstrated alterations in cerebral immune cells at postnatal day 60 (P60) typified by increased regulatory T cells (<i>p</i> < 0.01) and neutrophils (<i>p</i> < 0.05) in rats with POE compared to controls. Evaluation of serum revealed increased levels of IL-6 (<i>p</i> < 0.05) and CXCL1 (<i>p</i> < 0.05) at P21 in rats with POE compared to controls with no significant difference in cytokine or chemokine levels between the two groups at P60. Additionally, PBMCs isolated from rats with POE at P21 demonstrated baseline hypersecretion of IL-6 (<i>p</i> < 0.01) and SPIHR with increased levels of TNF-α (<i>p</i> < 0.05) and CXCL1 (<i>p</i> < 0.05) following stimulation with LPS. At P60, however, there was no significant difference found in cytokine or chemokine levels secreted by PBMCs isolated from rats with POE at baseline or with LPS stimulation when compared to controls. Taken together, these data demonstrate cerebral inflammation months after prenatal opioid exposure and long after the resolution of systemic inflammation and SPIHR seen at toddler age equivalent. Chronic alterations in the cerebral immune cell populations secondary to prenatal opioid exposure may underly long-term consequences of developmental brain injury including deficits in cognition and attention. These findings may be invaluable to further investigations of precise biomarkers of injury and targeted therapeutics for this vulnerable population.</p>","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9753176","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":"Noncoding RNA therapeutics for substance use disorder.","authors":"Seyed Afshin Seyednejad, Gregory C Sartor","doi":"10.3389/adar.2022.10807","DOIUrl":"10.3389/adar.2022.10807","url":null,"abstract":"<p><p>Although noncoding RNAs (ncRNAs) have been shown to regulate maladaptive neuroadaptations that drive compulsive drug use, ncRNA-targeting therapeutics for substance use disorder (SUD) have yet to be clinically tested. Recent advances in RNA-based drugs have improved many therapeutic issues related to immune response, specificity, and delivery, leading to multiple successful clinical trials for other diseases. As the need for safe and effective treatments for SUD continues to grow, novel nucleic acid-based therapeutics represent an appealing approach to target ncRNA mechanisms in SUD. Here, we review ncRNA processes implicated in SUD, discuss recent therapeutic approaches for targeting ncRNAs, and highlight potential opportunities and challenges of ncRNA-targeting therapeutics for SUD.</p>","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9808746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10489735","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":"Role of Gut Microbiota in Cannabinoid-Mediated Suppression of Inflammation.","authors":"Kontham Kulangara Varsha, Mitzi Nagarkatti, Prakash Nagarkatti","doi":"10.3389/adar.2022.10550","DOIUrl":"10.3389/adar.2022.10550","url":null,"abstract":"<p><p>Cannabinoids and the endocannabinoid system have been well established to play a crucial role in the regulation of the immune response. Also, emerging data from numerous investigations unravel the imperative role of gut microbiota and their metabolites in the maintenance of immune homeostasis and gut barrier integrity. In this review, we concisely report the immunosuppressive mechanisms triggered by cannabinoids, and how they are closely associated with the alterations in the gut microbiome and metabolome following exposure to endogenous or exogenous cannabinoids. We discuss how cannabinoid-mediated induction of microbial secondary bile acids, short chain fatty acids, and indole metabolites, produced in the gut, can suppress inflammation even in distal organs. While clearly, more clinical studies are necessary to establish the cross talk between exo- or endocannabinoid system with the gut microbiome and the immune system, the current evidence opens a new avenue of cannabinoid-gut-microbiota-based therapeutics to regulate immunological disorders.</p>","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10712108","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":"Alcohol Use Disorders and Their Harmful Effects on the Contractility of Skeletal, Cardiac and Smooth Muscles.","authors":"Jerusalem Alleyne, Alex M Dopico","doi":"10.3389/ADAR.2021.10011","DOIUrl":"10.3389/ADAR.2021.10011","url":null,"abstract":"<p><p>Alcohol misuse has deleterious effects on personal health, family, societal units, and global economies. Moreover, alcohol misuse usually leads to several diseases and conditions, including alcoholism, which is a chronic condition and a form of addiction. Alcohol misuse, whether as acute intoxication or alcoholism, adversely affects skeletal, cardiac and/or smooth muscle contraction. Ethanol (ethyl alcohol) is the main effector of alcohol-induced dysregulation of muscle contractility, regardless of alcoholic beverage type or the ethanol metabolite (with acetaldehyde being a notable exception). Ethanol, however, is a simple and \"promiscuous\" ligand that affects many targets to mediate a single biological effect. In this review, we firstly summarize the processes of excitation-contraction coupling and calcium homeostasis which are critical for the regulation of contractility in all muscle types. Secondly, we present the effects of acute and chronic alcohol exposure on the contractility of skeletal, cardiac, and vascular/ nonvascular smooth muscles. Distinctions are made between <i>in vivo</i> and <i>in vitro</i> experiments, intoxicating vs. sub-intoxicating ethanol levels, and human subjects vs. animal models. The differential effects of alcohol on biological sexes are also examined. Lastly, we show that alcohol-mediated disruption of muscle contractility, involves a wide variety of molecular players, including contractile proteins, their regulatory factors, membrane ion channels and pumps, and several signaling molecules. Clear identification of these molecular players constitutes a first step for a rationale design of pharmacotherapeutics to prevent, ameliorate and/or reverse the negative effects of alcohol on muscle contractility.</p>","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39927707","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":"Mechanisms Underlying the Anti-Suicidal Treatment Potential of Buprenorphine","authors":"Courtney M. Cameron, Steven J. Nieto, Lucienne Bosler, M. Wong, Isabel Bishop, Larissa J. Mooney, C. Cahill","doi":"10.3389/adar.2021.10009","DOIUrl":"https://doi.org/10.3389/adar.2021.10009","url":null,"abstract":"Death by suicide is a global epidemic with over 800 K suicidal deaths worlwide in 2012. Suicide is the 10th leading cause of death among Americans and more than 44 K people died by suicide in 2019 in the United States. Patients with chronic pain, including, but not limited to, those with substance use disorders, are particularly vulnerable. Chronic pain patients have twice the risk of death by suicide compared to those without pain, and 50% of chronic pain patients report that they have considered suicide at some point due to their pain. The kappa opioid system is implicated in negative mood states including dysphoria, depression, and anxiety, and recent evidence shows that chronic pain increases the function of this system in limbic brain regions important for affect and motivation. Additionally, dynorphin, the endogenous ligand that activates the kappa opioid receptor is increased in the caudate putamen of human suicide victims. A potential treatment for reducing suicidal ideation and suicidal attempts is buprenorphine. Buprenorphine, a partial mu opioid agonist with kappa opioid antagonist properties, reduced suicidal ideation in chronic pain patients with and without an opioid use disorder. This review will highlight the clinical and preclinical evidence to support the use of buprenorphine in mitigating pain-induced negative affective states and suicidal thoughts, where these effects are at least partially mediated via its kappa antagonist properties.","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"1995 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88115515","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 Genetically Modified Skin Graft for Treating Alcohol Use Disorder and/or Polysubstance Abuse With Cocaine.","authors":"Qingyao Kong, Xiaoyang Wu, Ming Xu","doi":"10.3389/adar.2021.10007","DOIUrl":"10.3389/adar.2021.10007","url":null,"abstract":"<p><p>Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We have developed and used a skin stem cell-based gene delivery platform and found that production of the glucagon-like peptide-1 (GLP1) from the grafted genetically modified skin reduced development and reinstatement of alcohol-induced drug-taking and seeking, voluntary oral alcohol consumption and alcohol-induced increase in dopamine (DA) levels in the nucleus accumbens (NAc). Moreover, we have developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Skin grafts-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by concurrent alcohol and cocaine injections. These results imply that gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.</p>","PeriodicalId":72092,"journal":{"name":"Advances in drug and alcohol research","volume":"1 1","pages":"10007"},"PeriodicalIF":0.0,"publicationDate":"2021-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42070961","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}