Addiction Biology最新文献

{"title":"Fentanyl-induced respiratory depression in rodents is inhibited by bioabsorbable, subcutaneous naltrexone implants at 3.5 months","authors":"Jeffrey D. Benner,&nbsp;Steven M. Cohen,&nbsp;Joseph A. Hollenbaugh,&nbsp;Marc Fishman","doi":"10.1111/adb.13350","DOIUrl":"10.1111/adb.13350","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants inhibit respiratory depression after an IV injection of fentanyl. Bioabsorbable implants fabricated from two different release-controlling polymers, poly-D-L-lactide (PDLLA) and polycaprolactone (PCL), alone (placebo) or containing NTX, were subcutaneously implanted in Sprague Dawley rats. After 3.5 months of implantation, the rodents were administered an IV bolus of fentanyl through the tail vein. The placebo implant rats received a dose of 4 micrograms (mcg) - (10 mcg/kg/dose), while the NTX implanted animals received a dose of 8 mcg (20 mcg/kg/dose). The <i>minimum active dose of fentanyl</i> that caused <i>a</i> &gt; 50 ± 2% depression in the respiration rate in the placebo implanted rodents was 4 mcg. The respiration rate of the placebo implanted rats dropped from 208 ± 14 breaths/minute at predose, to 84 ± 12 breaths/minute (<i>p</i> = 0.0003) at 2 min. In contrast, all NTX implanted animals easily tolerated <i>twice</i> the dose of 8 mcg of fentanyl without any significant reduction in respiration rate. The mean respiration rate = increased from 164 ± 22 breaths/minute at predose to 178 ± 17 breaths/minute (<i>p</i> = 0.24) at 2 min. The mean plasma concentrations of NTX, 3.5 months after implantation, ranged from 7.4 (±1.1) ng/mL to 80.3 (±37.5) ng/mL. Bioabsorbable implants containing NTX effectively blocked fentanyl-induced respiratory depression in rodents as compared with placebo implants, 3.5 months after implantation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136263667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The changes of intrinsic connectivity contrast in young smokers","authors":"Yang Zhou,&nbsp;Ting Xue,&nbsp;Yongxin Cheng,&nbsp;Juan Wang,&nbsp;Fang Dong,&nbsp;Shaodi Jia,&nbsp;Fan Zhang,&nbsp;Xiaoqing Wang,&nbsp;Xiaoqi Lv,&nbsp;Hongde Wang,&nbsp;Kai Yuan,&nbsp;Dahua Yu","doi":"10.1111/adb.13347","DOIUrl":"10.1111/adb.13347","url":null,"abstract":"<p>Previous studies demonstrated that reward circuit plays an important role in smoking. The differences of functional and structural connectivity were found among several brain regions such as thalamus and frontal lobe. However, few studies focused on functional connectivity (FC) in whole-brain voxel level of young smokers. In this study, intrinsic connectivity contrast (ICC) was used to perform voxel-based whole-brain analyses in 55 young smokers and 55 matched non-smokers to identify brain regions with significant group differences. ICC results showed that the connectivity of young smokers in medial frontal cortex (MedFC), supramarginal gyrus anterior division left (L_aSMG), central opercular cortex left (L_CO) and middle frontal gyrus left (L_MidFG) showed a significantly lower trend compared with the non-smokers. The seed-based FC analysis about MedFC indicated that young smokers showed reduced connectivity between the MedFC and left hippocampus, left amygdala compared to non-smokers. Correlation analysis showed that the ICC of MedFC in young smokers was significantly negatively correlated with Fagerstrom test for nicotine dependence (FTND) and Questionnaire on Smoking Urges (QSU). The FC between the MedFC and left hippocampus, left amygdala was significantly negatively correlated with Pack_years. The mediation analysis indicated that ICC of MedFC completely mediated FTND and QSU of young smokers. The results suggest that nicotine accumulation may affect the communication of the frontal lobe with the whole brain to some extent, leading to changes in smoking cravings. The above research also provides in-depth insights into the mechanism of adolescent smoking addiction and related intervention treatment.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136235060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent exposure to sucrose increases cocaine-mediated behaviours in adulthood via Smad3","authors":"Amy M. Gancarz,&nbsp;Raveena Parmar,&nbsp;Treefa Shwani,&nbsp;Moriah M. Cobb,&nbsp;Michelle N. Crawford,&nbsp;Jacob R. Watson,&nbsp;Lisa Evans,&nbsp;Michael A. Kausch,&nbsp;Craig T. Werner,&nbsp;David M. Dietz","doi":"10.1111/adb.13346","DOIUrl":"10.1111/adb.13346","url":null,"abstract":"<p>Adolescence, a critical period of developmental period, is marked by neurobiological changes influenced by environmental factors. Here, we show how exposure to sucrose, which is ubiquitously available in modern diets, results in changes in behavioural response to cocaine as an adult. Rats were given daily access to either 10% sucrose or water during the adolescent period (PND28–42). Following this period, rats are left undisturbed until they reach adulthood. In adulthood, rats were tested for (i) acquisition of a low dose of cocaine, (ii) progressive ratio (PR) test, and (iii) resistance to punished cocaine taking. Sucrose exposure resulted in significant alterations in all behavioural measures. To determine the neurobiological mechanisms leading to such behavioural adaptations, we find that adolescent sucrose exposure results in an upregulation of the transcription factor Smad3 in the nucleus accumbens (NAc) when compared with water-exposed controls. Transiently blocking the active form of this transcription factor (HSV-dnSmad3) during adolescence mitigated the enhanced cocaine vulnerability-like behaviours observed in adulthood. These findings suggest that prior exposure to sucrose during adolescence can heighten the reinforcing effects of cocaine. Furthermore, they identify the TGF-beta pathway and Smad3 as playing a key role in mediating enduring and long-lasting adaptations that contribute to sucrose-induced susceptibility to cocaine. Taken together, these results have important implications for development and suggest that adolescent sucrose exposure may persistently enhance the susceptibility to substance abuse.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136235053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal neuroanatomical patterns as potential diagnostic biomarkers for cocaine use disorder","authors":"Hui Xu,&nbsp;Cheng Xu,&nbsp;Yunyu Guo,&nbsp;Yike Hu,&nbsp;Guanghui Bai,&nbsp;Meimei Du","doi":"10.1111/adb.13348","DOIUrl":"10.1111/adb.13348","url":null,"abstract":"<p>Cocaine use disorder (CUD) is a global health problem with serious consequences for both individuals and society. Previous studies on abnormal anatomical patterns in CUD have mainly used voxel-based morphometry to investigate grey matter volume changes, while surface-based morphometry (SBM) has been found to provide detail information on cortical thickness (CT), surface area and cortical meancurve, which can contribute to a better understanding of structural brain changes associated with CUD. In this study, SBM was conducted to investigate abnormal neuroanatomical patterns in CUD and whether these abnormal patterns could be used as potential diagnostic biomarkers for CUD. Sixty-eight CUD individuals and 52 matched healthy controls were enrolled, and all participants performed once MRI scanning and clinical assessments. We found that CUD individuals exhibited altered morphological indicators across widespread brain regions and these abnormal anatomical alterations were significantly predictive of CUD status. Furthermore, the CT reduction of right insula was significantly associated with years of cocaine use in CUD. These findings revealed the association of abnormal anatomical patterns in specific brain regions in CUD, which further improve the understanding of CUD pathophysiology and provide the alternative diagnostic biomarkers for CUD.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The moderating effect of resting heart rate variability on the relationship between internet addiction tendency and brain morphology","authors":"Yuandong Zeng,&nbsp;Guo-Rong Wu,&nbsp;Yingying Xue,&nbsp;Chris Baeken,&nbsp;Luqing Wei","doi":"10.1111/adb.13340","DOIUrl":"10.1111/adb.13340","url":null,"abstract":"<p>Previous neuroimaging studies have investigated brain morphology associated with internet addiction tendency (IAT) in healthy subjects. However, whether resting vagally-mediated heart rate variability (HRV) exerting influences on the association of IAT and brain morphology remains unclear. This study used voxel-based morphometry (VBM) and multiple regression analyses to assess the interaction effect of IAT and resting vagally-mediated HRV on regional grey matter volumes in 82 healthy subjects. To further illustrate the observed interaction effect, the moderated hierarchical regression analysis was performed. The results showed that resting vagally-mediated HRV moderated the relationship between IAT scores and grey matter volume (GMV) in the precuneus and cerebellum. Specifically, individuals with higher resting vagally-mediated HRV showed a significant positive relationship between IAT scores and GMV in the precuneus, whereas individuals with lower resting vagally-mediated HRV showed a significant negative relationship between IAT scores and GMV in the precuneus. In addition, IAT scores were negatively correlated with GMV in the cerebellum among individuals with lower resting vagally-mediated HRV, but not among individuals with higher resting vagally-mediated HRV. These findings have demonstrated a moderating role of resting vagally-mediated HRV on the association of IAT and brain morphology.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regaining control over opioid use? The potential application of auricular transcutaneous vagus nerve stimulation to improve opioid treatment in China","authors":"Lorenza Colzato,&nbsp;Julia Elmers,&nbsp;Xiaolei Xu,&nbsp;Qiang Zhou,&nbsp;Bernhard Hommel,&nbsp;Christian Beste","doi":"10.1111/adb.13343","DOIUrl":"10.1111/adb.13343","url":null,"abstract":"<p>Opioid use disorder (OUD) is a critical problem in China and is accompanied by depression and deficits in cognitive control. In China, the most successful intervention for OUD is the community drug rehabilitation where methadone maintenance treatment (MMT) plays a key role. Even though methadone for the treatment of OUD can be helpful, it can cause severe somatic side-effects, which limit its effectivity. Even worse, it can have detrimental effects on cognitive control, which is crucial to regain control over drug intake. Here, we consider the potential use of auricular transcutaneous vagus nerve stimulation (atVNS) as an addition to MMT for opioid withdrawal treatment. Compared to other non-invasive brain stimulation methods, atVNS also targets the locus coeruleus (LC) important for noradrenaline (NA) synthesis. NA is an essential neurotransmitter impacted in opioid withdrawal and also critically involved in cognitive control processes. Its ADD-ON to MMT might be a useful mean to improve mood and enhance cognitive control processes impacted in OUD. We discuss the translational advantages of atVNS in China such as the cultural acceptance of the modality of treatment similar to electroacupuncture. Additionally, the wearability of the ear electrode and at-home self-administration without intense medical supervision makes of atVNS a useful tool to enhance clinical and cognitive outcomes especially in everyday life situation. We discuss how atVNS can be integrated in tele-medical health approaches allowing that innovative treatments can widely be disseminated and continued even in situations of restricted medical access.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced expression of parvalbumin and perineuronal nets in the medial prefrontal cortex after extended-access cocaine self-administration in rats","authors":"Jereme C. Wingert,&nbsp;Jonathan N. Anguiano,&nbsp;Jonathan D. Ramos,&nbsp;Jordan M. Blacktop,&nbsp;Angela E. Gonzalez,&nbsp;Lynn Churchill,&nbsp;Barbara A. Sorg","doi":"10.1111/adb.13334","DOIUrl":"10.1111/adb.13334","url":null,"abstract":"<p>The medial prefrontal cortex (mPFC) drives cocaine-seeking behaviour in rodent models of cocaine use disorder. Parvalbumin (PV)-containing GABAergic interneurons powerfully control the output of the mPFC, yet few studies have focused on how these neurons modulate cocaine-seeking behaviour. Most PV neurons are surrounded by perineuronal nets (PNNs), which regulate the firing of PV neurons. We examined staining intensity and number of PV and PNNs after long-access (6 h/day) cocaine self-administration in rats followed by either 8–10 days extinction ± cue-induced reinstatement or short-term (1–2 days) or long-term (30–31 days) abstinence ± cue-induced reinstatement. The intensity of PNNs was increased in the prelimbic and infralimbic PFC after long-term abstinence in the absence of cue reinstatement and after cue reinstatement following both daily extinction sessions and after a 30-day abstinence period. PV intensity was increased after 30 days of abstinence in the prelimbic but not infralimbic PFC. Enzymatic removal of PNNs with chondroitinase ABC (ABC) in the prelimbic PFC did not prevent incubation of cue-induced reinstatement but decreased cocaine-seeking behaviour at both 2 and 31 days of abstinence, and this decrease at 31 days was accompanied by reduced c-Fos levels in the prelimbic PFC. Increases in PNN intensity have generally been associated with the loss of plasticity, suggesting that the persistent and chronic nature of cocaine use disorder may in part be attributed to long-lasting increases in PNN intensity that reduce the ability of stimuli to alter synaptic input to underlying PV neurons.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant functional brain network organization is associated with relapse during 1-year follow-up in alcohol-dependent patients","authors":"Justin Böhmer,&nbsp;Pablo Reinhardt,&nbsp;Maria Garbusow,&nbsp;Michael Marxen,&nbsp;Michael N. Smolka,&nbsp;Ulrich S. Zimmermann,&nbsp;Andreas Heinz,&nbsp;Danilo Bzdok,&nbsp;Eva Friedel,&nbsp;Johann D. Kruschwitz,&nbsp;Henrik Walter","doi":"10.1111/adb.13339","DOIUrl":"10.1111/adb.13339","url":null,"abstract":"<p>Alcohol dependence (AD) is a debilitating disease associated with high relapse rates even after long periods of abstinence. Thus, elucidating neurobiological substrates of relapse risk is fundamental for the development of novel targeted interventions that could promote long-lasting abstinence. In the present study, we analysed resting-state functional magnetic resonance imaging (rsfMRI) data from a sample of recently detoxified patients with AD (<i>n</i> = 93) who were followed up for 12 months after rsfMRI assessment. Specifically, we employed graph theoretic analyses to compare functional brain network topology and functional connectivity between future relapsers (REL, <i>n</i> = 59), future abstainers (ABS, <i>n</i> = 28) and age- and gender-matched controls (CON, <i>n</i> = 83). Our results suggest increased whole-brain network segregation, decreased global network integration and overall blunted connectivity strength in REL compared with CON. Conversely, we found evidence for a comparable network architecture in ABS relative to CON. At the nodal level, REL exhibited decreased integration and decoupling between multiple brain systems compared with CON, encompassing regions associated with higher-order executive functions, sensory and reward processing. Among patients with AD, increased coupling between nodes implicated in reward valuation and salience attribution constitutes a particular risk factor for future relapse. Importantly, aberrant network organization in REL was consistently associated with shorter abstinence duration during follow-up, portending to a putative neural signature of relapse risk in AD. Future research should further evaluate the potential diagnostic value of the identified changes in network topology and functional connectivity for relapse prediction at the individual subject level.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Executive function deficit in betel quid-dependence: Evidence from functional and effective connectivity of executive control network","authors":"Meiting Ban,&nbsp;Dongcui Wang,&nbsp;Jincheng He,&nbsp;Xueling Zhu,&nbsp;Fulai Yuan","doi":"10.1111/adb.13341","DOIUrl":"10.1111/adb.13341","url":null,"abstract":"<p>Betel quid (BQ) ranks fourth in global self-administered psychoactive agents, after caffeine, alcohol and nicotine, with 600 million consumers. Patients with BQ dependence (BQD) disorder demonstrate deficits in executive function. However, the neural correlates of the resting-state executive control network (ECN) and BQD-related pathopsychological characteristics still remain unclear. The present study aimed to assess the functional and effective connectivity of the ECN using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty-five BQD individuals and 54 healthy controls (HCs) were recruited in this study. The executive function of all participants was tested by three tasks. Independent component and Granger causal analysis were employed to investigate the functional connectivity within ECN and ECN-related directional effective connectivity, separately. Behavioural results suggested a marked deficit of executive function in BQD individuals. Compared with HCs, BQD individuals showed overall weaker functional connectivity in the ECN, mainly including dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (IPL) and middle frontal gyrus (MFG). We observed decreased outflow of information from the right DLPFC and IPL to the precentral/pre-supplement motor area (SMA) and increased outflow of information from the MFG to the middle occipital gyrus in BQD individuals. Correlation analysis revealed that the effective connectivity from IPL to precentral/pre-SMA was negatively correlated to the BQD scales in BQD individuals. Our findings revealed impaired executive function, functional connectivity of the ECN and causal interaction between networks in patients with BQD. These results could potentially direct future targets for the prevention and intervention of BQD.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased AGE–RAGE axis stress in methamphetamine abuse and methamphetamine-induced psychosis: Associations with oxidative stress and increased atherogenicity","authors":"Hussein Kadhem Al-Hakeim,&nbsp;Mazin Fadhil Altufaili,&nbsp;Amer Fadhil Alhaideri,&nbsp;Abbas F. Almulla,&nbsp;Shatha Rouf Moustafa,&nbsp;Michael Maes","doi":"10.1111/adb.13333","DOIUrl":"10.1111/adb.13333","url":null,"abstract":"<p>Methamphetamine (MA)-induced psychosis (MIP) is associated with increased oxidative toxicity (especially lipid peroxidation) and lowered antioxidant defences. Advanced glycation end products (AGEs) cause oxidative stress upon ligand binding to AGE receptors (RAGEs). There is no data on whether MA use may cause AGE–RAGE stress or whether the latter is associated with MIP. This case–control study recruited 60 patients with MA use disorder and 30 normal controls and measured serum levels of oxidative stress toxicity (OSTOX, lipid peroxidation), antioxidant defences (ANTIOX), magnesium, copper, atherogenicity, AGE and soluble RAGE (sRAGE) and computed a composite reflecting AGE–RAGE axis activity. MA dependence and use were associated with elevated levels of AGE, sRAGE, OSTOX/ANTIOX, Castelli Risk Index 1 and atherogenic index of plasma. Increased sRAGE concentrations were strongly correlated with dependence severity and MA dose. Increased AGE–RAGE stress was correlated with OSTOX, OSTOX/ANTIOX and MA-induced intoxication symptoms, psychosis, hostility, excitement and formal thought disorders. The regression on AGE–RAGE, the OSTOX/ANTIOX ratio, decreased magnesium and increased copper explained 54.8% of the variance in MIP symptoms, and these biomarkers mediated the effects of increasing MA concentrations on MIP symptoms. OSTOX/ANTIOX, AGE–RAGE and insufficient magnesium were found to explain 36.0% of the variance in the atherogenicity indices. MA causes intertwined increases in AGE–RAGE axis stress and oxidative damage, which together predict the severity of MIP symptoms and increased atherogenicity.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"28 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41140307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}