Journal of Drug and Alcohol Research最新文献

{"title":"Temporal Requirement for the Protective Effect of Dietary Cholesterol against Alcohol-Induced Vasoconstriction.","authors":"Olga Seleverstov,&nbsp;Kelsey North,&nbsp;Maria Simakova,&nbsp;Shivantika Bisen,&nbsp;Alexandra Bickenbach,&nbsp;Zoran Bursac,&nbsp;Alex M Dopico,&nbsp;Anna N Bukiya","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Moderate-to-heavy episodic alcohol drinking resulting in 30-80 mM of ethanol in blood constricts cerebral arteries and constitutes a risk factor for cerebrovascular disease. Alcohol-induced constriction of cerebral arteries <i>in vivo</i> and <i>ex vivo</i> has been shown to be blunted by dietary cholesterol (CLR) in a rat model of a high-CLR diet. Such protection has been proposed to arise from the high-CLR diet-driven increase in blood CLR levels and accompanying buildup of CLR within the cerebral artery smooth muscle. Here we used a rat model of high-CLR feeding <i>in vivo</i> and pressurized cerebral arteries <i>ex vivo</i> to examine whether the degree and time-course of alcohol-induced constriction are related to blood CLR levels. We demonstrate that subjecting young (3 weeks-old, 50 g) male Sprague-Dawley rats to a high- CLR feeding up to 41 weeks, resulted in an age-dependent increase in total blood CLR levels, when compared to those of age-matched rats on isocaloric (control) chow. This increase was paralleled by a high-CLR diet-driven elevation of blood low-density lipoproteins whereas high-density lipoprotein levels matched those of age-matched, chow-fed controls. Alcohol-induced constriction was only blunted by high-CLR dietary intake when high-CLR chow was taken for up to 8-12 and 18-23 weeks. However, alcohol-constriciton was not blunted when high-CLR chow intake lasted for longer times, such as 28-32 and 38-41 weeks. Thus, alcohol-induced constriction of rat middle cerebral arteries did not critically depend on the total blood CLR levels. Alcohol-induced constriction seemed unrelated to the natural, progressive elevation of the total blood CLR level in control- or high-CLR-fed animals over time. Thus, neither the exogenously nor endogenously driven increases in blood CLR could predict cerebral artery susceptibility to alcohol-induced constriction. However, we identified a temporal requirement for the protective effect of dietary CLR against alcohol, that could be governed by the young age of the high- CLR chow recipients (3 weeks of age) and/or the short duration of high-CLR chow feeding lasting for up to 23 weeks.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25328951","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":"Bi-directional Acceleration of Alcohol Use and Opioid Use Disorder","authors":"Wenfei Huang, Erika P. Penaherrera, Danaika F. Desir, Dominick L. Gamarro, J. Cottrell, Tinchun Chu, Sulie L. Chang","doi":"10.4303/JDAR/236084","DOIUrl":"https://doi.org/10.4303/JDAR/236084","url":null,"abstract":"Alcohol is the most widely used addictive substance. Severe alcohol abuse is diagnosed as “alcohol use disorder” (AUD). A common and harmful drinking pattern is binge drinking that elevates a person’s blood alcohol concentration to ≥ 0.08%. Such drinking may be an early indicator of AUD. Opioid misuse and dependence have become worldwide crises. Patterned consumption of various opioids can develop into opioid use disorder (OUD). An intertwined epidemic exists between opioid abuse, alcohol addiction, and binge drinking. Currently, studies on the interaction of AUD and OUD are limited and the underlying mechanisms linking these disorders remains unclear. We reviewed studies on AUD and OUD and utilized Ingenuity Pathway Analysis (IPA) to identify mechanisms of AUD and OUD interaction and potential gene targets for therapeutic agents. According to IPA Canonical Pathways Analysis, Gamma-aminobutyric Acid (GABA) Receptor Signaling, Neuroinflammation Signaling Pathway, Opioid Signaling Pathway and Dopamine-DARPP32 Feedback in cAMP Signaling are potential contributors to the interaction of AUD and OUD.","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73864346","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":"Bi-directional Acceleration of Alcohol Use and Opioid Use Disorder.","authors":"Wenfei Huang,&nbsp;Erika P Penaherrera,&nbsp;Danaika F Desir,&nbsp;Dominick L Gamarro,&nbsp;Jessica Cottrell,&nbsp;Tinchun Chu,&nbsp;Sulie L Chang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alcohol is the most widely used addictive substance. Severe alcohol abuse is diagnosed as \"alcohol use disorder\" (AUD). A common and harmful drinking pattern is binge drinking that elevates a person's blood alcohol concentration to ≥ 0.08%. Such drinking may be an early indicator of AUD. Opioid misuse and dependence have become worldwide crises. Patterned consumption of various opioids can develop into opioid use disorder (OUD). An intertwined epidemic exists between opioid abuse, alcohol addiction, and binge drinking. Currently, studies on the interaction of AUD and OUD are limited and the underlying mechanisms linking these disorders remains unclear. We reviewed studies on AUD and OUD and utilized Ingenuity Pathway Analysis (IPA) to identify mechanisms of AUD and OUD interaction and potential gene targets for therapeutic agents. According to IPA Canonical Pathways Analysis, Gamma-aminobutyric Acid (GABA) Receptor Signaling, Neuroinflammation Signaling Pathway, Opioid Signaling Pathway and Dopamine-DARPP32 Feedback in cAMP Signaling are potential contributors to the interaction of AUD and OUD.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962523","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":"Both Ketamine and NBQX Attenuate Alcohol-Withdrawal Induced Depression in Male Rats.","authors":"Bruk Getachew, Yousef Tizabi","doi":"10.4303/jdar/236069","DOIUrl":"10.4303/jdar/236069","url":null,"abstract":"<p><p>The co-morbidity between heavy drinking and depression can negatively influence successful cessation of alcohol use. Since ketamine, a glutamatergic NMDA receptor antagonist, has shown promise as a quick-acting antidepressant, we studied its effects specifically on alcohol withdrawal-induced depression. We also evaluated the effects of NBQX an AMPA/kainate receptor antagonist, because some of the effects of ketamine are proposed to be indirectly mediated through these receptors. Adult male Wistar rats were exposed daily to ethanol via inhalation chambers 4 h/day for 7 days (blood alcohol concentration=160 mg%), followed by daily intraperitoneal injections of ketamine (2.5 mg/kg), NBQX (5mg/kg), alone or in combination. Eighteen hours later, open field locomotor activity (OFLA) followed by forced swim test (FST) were performed. The animals were sacrificed 2 h later for evaluation of brain-derived neurotrophic factor (BDNF) in the hippocampus. Alcohol withdrawal did not affect OFLA, but caused an increase in immobility in FST, suggesting induction of \"depressive-like\" helplessness. Both ketamine and NBQX normalized the swimming score in FST. The combination of the two drugs, however, cancelled each other's effect. Parallel to these behavioral observations, both ketamine and NBQX normalized the reduction in hippocampal BDNF caused by alcohol withdrawal. Here also, the combination of the two drugs cancelled each other's effect. These results suggest that either NMDA or AMPA/kainate receptor antagonists, acting at least partially through hippocampal BDNF, may be of therapeutic potential in alcohol use disorder.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5a/f2/nihms-1020013.PMC6483102.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37369112","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":"Gestational Age-Dependent Interplay between Endocannabinoid Receptors and Alcohol in Fetal Cerebral Arteries.","authors":"Maria Simakova, Ana Tobiasz, Ryan D Sullivan, Shivantika Bisen, Jose Duncan, J Pierce Sullivan, Steven Davison, Danielle L Tate, Stacey Barnett, Giancarlo Mari, Alex M Dopico, Anna N Bukiya","doi":"10.4303/jdar/236068","DOIUrl":"10.4303/jdar/236068","url":null,"abstract":"<p><p>Alcohol (ethanol) is one of the most widely consumed drugs. Alcohol consumption by pregnant women may result in a range of fetal abnormalities termed fetal alcohol spectrum disorders (FASDs). The cerebrovascular system is emerging as a critical target of alcohol in the developing brain. We recently showed that three episodes of prenatal alcohol exposure resulting in 80 mg/dL alcohol in maternal blood during mid-pregnancy up-regulated anandamide-induced dilation of fetal cerebral arteries. Moreover, ethanol dilated fetal cerebral arteries via cannabinoid (CB) receptors. Whether a critical role of fetal cerebral artery CB system in responses to alcohol was maintained throughout the gestation, remains unknow.</p><p><strong>Main methods: </strong>Pregnant baboons (second trimester equivalent) were subjected to three episodes of either alcohol or control drink infusion via gavage. Cerebral arteries from mothers and near-term female fetuses were <i>in vitro</i> pressurized for diameter monitoring.</p><p><strong>Key findings: </strong>Near-term fetal and maternal arteries exhibited similar ability to develop myogenic tone, to constrict in presence of 60 mM KCl, and to respond to 10 µM anandamide. Fetal and maternal arteries largely failed to dilate in presence of 63 mM ethanol. No differences were detected between arteries from control and alcohol-exposed baboon donors. Therefore, previously observed ethanol-induced dilation of fetal cerebral arteries and up-regulation of CB components in response to fetal alcohol exposure during mid-pregnancy was transient and disappeared by near-term.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37214235","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":"Prenatal Alcohol Exposure, Anesthesia, and Fetal Loss in Baboon Model of Pregnancy.","authors":"Kelsey North,&nbsp;Ana Tobiasz,&nbsp;Ryan D Sullivan,&nbsp;Zoran Bursac,&nbsp;Jose Duncan,&nbsp;J Pierce Sullivan,&nbsp;Steven Davison,&nbsp;Danielle L Tate,&nbsp;Stacey Barnett,&nbsp;Giancarlo Mari,&nbsp;Anna N Bukiya","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Approximately half of pregnant women engage in alcohol consumption some time during pregnancy. On the other hand, a small percentage of pregnant women undergo surgery and anesthesia at some time during pregnancy. In emergencies, anesthesia has to be administered to patients who are under alcohol intoxication. Anesthetic management during pregnancy while patients are intoxicated with alcohol is challenging. Here, we utilized a retrospective analysis of data available from 17 pregnant baboons that underwent anesthesia with alcohol exposure during mid-pregnancy. The analysis was designed to answer three questions: whether maternal vital signs remained stable under anesthesia combined with alcohol, whether maternal vital signs that were routinely monitored under anesthesia could serve as predictor(s) of fetal loss, and what the impact of the combined application of anesthesia and alcohol was on fetal loss. For the purpose of this retrospective analysis, we utilized vital sign (heart and respiratory rates, temperature, oxygen, carbon dioxide, systolic and diastolic blood pressure) and pregnancy outcome (miscarriage versus fetal survival through second trimester-equivalent of human pregnancy) records from 17 pregnant baboons that underwent gastric infusion of either control or alcohol-containing drink under isoflurane anesthesia during the second trimester-equivalent of human pregnancy. Half of the dams underwent a brief prior anesthetic episode for the purpose of gestational age confirmation. Thus, in our analysis, baboons were divided into four groups: \"Control\" without prior anesthesia, \"Control\" with prior anesthesia, \"Alcohol\" without prior anesthesia, and \"Alcohol\" with prior anesthesia. We did not detect any maternal vital sign in any of the groups that would be predictive of a fetal loss. However, prior anesthesia predisposed dams to the risk of lowering maternal systolic blood pressure and to a significant decrease in maternal oxygen level during the combined application of anesthesia and alcohol. Conceivably, our data showed the largest fetal loss in this group. The disruptive nature of anesthesia and alcohol on maternal vital parameters warns against the use of anesthesia in combination with alcohol during pregnancy.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36875103","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":"Prenatal Alcohol Exposure, Anesthesia, and Fetal Loss in Baboon Model of Pregnancy","authors":"Kelsey C. North, A. Tobiasz, Ryan D. Sullivan, Z. Bursac, J. Duncan, J. P. Sullivan, Steven Davison, D. Tate, Stacey Barnett, G. Mari, A. Bukiya","doi":"10.4303/JDAR/236064","DOIUrl":"https://doi.org/10.4303/JDAR/236064","url":null,"abstract":"Approximately half of pregnant women engage in alcohol consumption some time during pregnancy. On the other hand, a small percentage of pregnant women undergo surgery and anesthesia at some time during pregnancy. In emergencies, anesthesia has to be administered to patients who are under alcohol intoxication. Anesthetic management during pregnancy while patients are intoxicated with alcohol is challenging. Here, we utilized a retrospective analysis of data available from 17 pregnant baboons that underwent anesthesia with alcohol exposure during mid-pregnancy. The analysis was designed to answer three questions: whether maternal vital signs remained stable under anesthesia combined with alcohol, whether maternal vital signs that were routinely monitored under anesthesia could serve as predictor(s) of fetal loss, and what the impact of the combined application of anesthesia and alcohol was on fetal loss. For the purpose of this retrospective analysis, we utilized vital sign (heart and respiratory rates, temperature, oxygen, carbon dioxide, systolic and diastolic blood pressure) and pregnancy outcome (miscarriage versus fetal survival through second trimester-equivalent of human pregnancy) records from 17 pregnant baboons that underwent gastric infusion of either control or alcohol-containing drink under isoflurane anesthesia during the second trimester-equivalent of human pregnancy. Half of the dams underwent a brief prior anesthetic episode for the purpose of gestational age confirmation. Thus, in our analysis, baboons were divided into four groups: “Control” without prior anesthesia, “Control” with prior anesthesia, “Alcohol” without prior anesthesia, and “Alcohol” with prior anesthesia. We did not detect any maternal vital sign in any of the groups that would be predictive of a fetal loss. However, prior anesthesia predisposed dams to the risk of lowering maternal systolic blood pressure and to a significant decrease in maternal oxygen level during the combined application of anesthesia and alcohol. Conceivably, our data showed the largest fetal loss in this group. The disruptive nature of anesthesia and alcohol on maternal vital parameters warns against the use of anesthesia in combination with alcohol during pregnancy.","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75581313","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 Hepatic Steatosis: A Comparative Study to Identify Possible Indicator(s) of Alcoholic Fatty Liver Disease.","authors":"Harshica Fernando,&nbsp;Kamlesh K Bhopale,&nbsp;Shakuntala S Kondraganti,&nbsp;Bhupendra S Kaphalia,&nbsp;G A Shakeel Ansari","doi":"10.4303/jdar/236040","DOIUrl":"https://doi.org/10.4303/jdar/236040","url":null,"abstract":"<p><strong>Background: </strong>Fatty liver is an early sign of both nonalcoholic and alcoholic fatty liver diseases. Ethanol feeding using a Lieber-DeCarli liquid diet (LD) model which contains 35% fat to rats or mice is a well-established model for alcoholic fatty liver. However, LD diet alone can also induce fatty liver and its differential metabolic profile may be able to differentiate steatosis induced by LD versus LD plus ethanol.</p><p><strong>Purpose: </strong>We investigated the lipidomic differences in the livers of Sprague-Dawley (SD) rats fed a pellet diet (PD), LD and liquid ethanol diet (LED) for six weeks.</p><p><strong>Study design: </strong>Male Sprague Dawley rats were fed with nonalcoholic diets PD, LD or LED (ethanol in LD) for six weeks. Lipids were extracted and analyzed by nuclear magnetic resonance (NMR)- based metabolomics. The NMR data obtained was analyzed by multivariate Principal Component Analysis (PCA) and Spotfire DecisionSite 9.0 software to compare PD versus LD and LD versus LED groups.</p><p><strong>Results: </strong>PCA of the NMR spectral data of livers of both comparisons showed a clear separation of PD from LD group and LD from LED group indicating differences in lipid profiles which corresponded with changes in total lipid weights. LD showed increases for cholesterol, esterified cholesterol, cholesterol acetate and triglycerides with decreases for fatty acyl chain, diallylic and allylic protons, while the LED showed increases in esterified cholesterol, cholesterol acetate, fatty acid methyl esters, allylic protons and some triglyceride protons with decreases in free cholesterol and phosphatidylcholine (PC).</p><p><strong>Conclusion: </strong>Our data suggest that altered lipid signature or PC levels could be an indicator to differentiate between nonalcoholic versus alcoholic fatty liver.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483099/pdf/nihms-995405.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37369110","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":"Ketamine Differentially Attenuates Alcohol Intake in Male Versus Female Alcohol Preferring (P) Rats.","authors":"Amir H Rezvani, Edward D Levin, Marty Cauley, Bruk Getachew, Yousef Tizabi","doi":"10.4303/jdar/236030","DOIUrl":"10.4303/jdar/236030","url":null,"abstract":"<p><strong>Background: </strong>Although various pharmacological tools in combating addiction to alcohol are available, their efficacy is limited. Hence, there is a critical need for development of more effective medications. Recent advances in the field have identified the glutamatergic system as a potential novel target for intervention in addictive behaviors.</p><p><strong>Purpose: </strong>Hence, we evaluated the effects of acute administration of low (subanesthetic) doses of ketamine, an NMDA receptor antagonist, on alcohol intake and alcohol preference in both male and female rats.</p><p><strong>Study design: </strong>Adult alcohol preferring (P) rats were exposed to two-bottle choice (ethanol 10% and water) for at least three weeks following a nine-day training period and the effects of various doses of ketamine (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, injected subcutaneously, SC) on consumption of alcohol over various time periods during a 24 h interval were measured.</p><p><strong>Results: </strong>Our results indicate that ketamine treatment significantly reduced both alcohol intake and preference in a time- and dose-dependent manner in both sexes. Moreover, a differential sensitivity between the sexes was observed. Thus, although alcohol intake was higher in males, female rats responded much more strongly to the highest dose of ketamine than males in the initial time periods.</p><p><strong>Conclusion: </strong>It is concluded that glutamatergic receptor manipulations may be of therapeutic potential in addiction to alcohol and that different sexes may respond differentially to such treatments.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35806550","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-Induced Increases in Inflammatory Cytokines Are Attenuated by Nicotine in Region-Selective Manner in Male Rats.","authors":"Olubukola Kalejaiye, Bruk Getachew, Clifford L Ferguson, Robert E Taylor, Yousef Tizabi","doi":"10.4303/jdar/236036","DOIUrl":"10.4303/jdar/236036","url":null,"abstract":"<p><strong>Background: </strong>Heavy use of alcohol is commonly associated with heavy smoking (nicotine intake). Although many factors, including mood effects of these two drugs may contribute to their co-use, the exact neurobiological underpinnings are far from clear. It is well known that chronic alcohol exposure induces neuroinflammation that may precipitate depressive-like behavior, which is considered an important factor in alcohol relapse. Nicotine, on the other hand, possesses anti-inflammatory and antidepressant effects.</p><p><strong>Purpose: </strong>In this study, we sought to determine which proinflammatory markers may be associated with the depressogenic effects of chronic alcohol and whether nicotine pretreatment may normalize these changes.</p><p><strong>Study design: </strong>For this purpose, we treated adult male Wistar rats with alcohol (1.0 g/kg, IP), nicotine (0.3 mg/kg, IP) or their combination once daily for 14 days. Two prominent proinflammatory cytokines (IL-1<i>β</i> and TNF-<i>α</i>) in two primary brain regions, namely the hippocampus and frontal cortex that are intimately involved in mood regulation, were evaluated.</p><p><strong>Results: </strong>Chronic alcohol resulted in increases in both cytokines in both regions as determined by Western blot. Nicotine completely blocked alcohol-induced effects in the hippocampus, but not in the frontal cortex. These data suggest that nicotine may mitigate the inflammatory effects of alcohol in brain-selective region. Hence, the previously observed depressogenic effects of alcohol and the antidepressant effects of nicotine may at least be partially mediated through manipulations of proinflammatory cytokines in the hippocampus.</p><p><strong>Conclusion: </strong>These findings suggest possible therapeutic potential of anti-inflammatory cytokines in combating alcohol-induced depression and/or relapse.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35806552","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}