Addiction Biology最新文献

{"title":"N-acetylcysteine as a treatment for substance use cravings: A meta-analysis","authors":"Emma L. Winterlind,&nbsp;Samantha G. Malone,&nbsp;Michael R. Setzer,&nbsp;Mikela A. Murphy,&nbsp;David Saunders,&nbsp;Joshua C. Gray","doi":"10.1111/adb.70001","DOIUrl":"https://doi.org/10.1111/adb.70001","url":null,"abstract":"<p>N-acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta-analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of this updated meta-analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with SUD and (2) explore subgroup differences, risk of bias and publication bias across trials. Database searches of PubMed, Cochrane Library and ClinicalTrials.gov were conducted in June and July of 2023 to identify relevant randomized control trials (RCTs). The meta-analysis consisted of 9 trials which analysed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta-analysis, subgroup analyses and leave-one-out analyses were conducted to examine the treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests and funnel plot tests were conducted to examine the risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta-analysis (SMD = 0.189, 95% CI = −0.015–0.393). Heterogeneity was very high in the meta-analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. Overall, our findings are contrary to those of prior meta-analyses, suggesting a limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta-analytic outcomes.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665907","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 potential mechanisms underlying the effect of acute alcohol use on duration perception","authors":"Yunpeng Liu,&nbsp;Minghui Lu,&nbsp;Huazhan Yin,&nbsp;Chun Yang,&nbsp;Dehua Wu","doi":"10.1111/adb.70004","DOIUrl":"10.1111/adb.70004","url":null,"abstract":"<p>Acute alcohol consumption has been found to cause duration perception distortions, but the directions of these distortions are not consistent. The mechanisms underlying this effect are also unclear. The present study seeks to elucidate the effect of acute alcohol consumption on duration perception and the mechanisms involved. Forty-one participants in the placebo group and 40 in the alcohol group completed time bisection tasks, attentional network tests, digit span backward tests and arousal reports to evaluate their duration perception, attentional network, working memory capacity and arousal. The results showed that the alcohol group overestimated duration compared to the placebo group. The alcohol group also showed increased arousal, impaired executive control of attention and reduced working memory capacity. Arousal mediated the effect of acute alcohol consumption on duration perception, whilst working memory capacity masked this effect. The findings are discussed based on the Scalar Timing Model and the Cognitive Resource Allocation Model.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631120","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":"Key insights into cannabis-cancer pathobiology and genotoxicity","authors":"Albert Stuart Reece,&nbsp;Gary Kenneth Hulse","doi":"10.1111/adb.70003","DOIUrl":"10.1111/adb.70003","url":null,"abstract":"<p>Whilst mitochondrial inhibition and micronuclear fragmentation are well established features of the cannabis literature mitochondrial stress and dysfunction has recently been shown to be a powerful and direct driver of micronucleus formation and chromosomal breakage by multiple mechanisms. In turn genotoxic damage can be expected to be expressed as increased rates of cancer, congenital anomalies and aging; pathologies which are increasingly observed in modern continent-wide studies. Whilst cannabinoid genotoxicity has long been essentially overlooked it may in fact be all around us through the rapid induction of aging of eggs, sperm, zygotes, foetus and adult organisms with many lines of evidence demonstrating transgenerational impacts. Indeed this multigenerational dimension of cannabinoid genotoxicity reframes the discussion of cannabis legalization within the absolute imperative to protect the genomic and epigenomic integrity of multiple generations to come.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631108","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":"Multi-domain predictors of grip strength differentiate individuals with and without alcohol use disorder","authors":"Magdalini Paschali,&nbsp;Qingyu Zhao,&nbsp;Stephanie A. Sassoon,&nbsp;Adolf Pfefferbaum,&nbsp;Edith V. Sullivan,&nbsp;Kilian M. Pohl","doi":"10.1111/adb.70007","DOIUrl":"10.1111/adb.70007","url":null,"abstract":"<p>Grip strength is considered one of the simplest and reliable indices of general health. Although motor ability and strength are commonly affected in people with alcohol use disorder (AUD), factors predictive of grip strength decline in AUD have not been investigated. Here, we employed a data-driven analysis predicting grip strength from measurements in 53 controls and 110 AUD participants, 53 of whom were comorbid with HIV infection. Controls and AUD were matched on sex, age, and body mass index. Measurements included commonly available metrics of brain structure, neuropsychological functioning, behavioural status, haematological and health status, and demographics. Based on 5-fold stratified cross-validation, a machine learning approach predicted grip strength separately for each cohort. The strongest (top 10%) predictors of grip were then tested against grip strength with correlational analysis. Leading grip strength predictors for both cohorts were cerebellar volume and mean corpuscular haemoglobin concentration. Predictors specific to controls were Backwards Digit Span, precentral gyrus volume, diastolic blood pressure, and mean platelet volume, which together significantly predicted grip strength (<i>R</i>² = 0.255, <i>p</i> = 0.001). Unique predictors for AUD were comorbidity for HIV infection, social functioning, insular volume, and platelet count, which together significantly predicted grip strength (<i>R</i>² = 0.162, <i>p</i> = 0.002). These cohort-specific predictors were doubly dissociated. Salient predictors of grip strength differed by diagnosis with only modest overlap. The constellation of cohort-specific predictive measurements of compromised grip strength provides insight into brain, behavioural, and physiological factors that may signal subtly affected yet treatable processes of physical decline and frailty.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631119","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":"Integration of pharmacochemistry, pharmacodynamics and metabolomics to reveal active ingredients and mechanism of Nan Bao detox capsule alleviating methamphetamine addiction","authors":"Bin Zhang,&nbsp;Chen Yang,&nbsp;Yuxiao Zheng,&nbsp;Xinliang Li,&nbsp;Xingguo Wang,&nbsp;Li Yuehui","doi":"10.1111/adb.70005","DOIUrl":"10.1111/adb.70005","url":null,"abstract":"<p>Nan Bao detox capsule (NBDC), derived from ancient Chinese opioid detox protocols, shows promising therapeutic potential in substance abuse disorders, particularly for attenuating methamphetamine (MA) addiction. This study aimed to identify active ingredients, evaluate therapeutic efficacy in an MA addiction rat model and delineate pharmacodynamic mechanisms using metabolomics. In vitro phytochemical profiling characterized 258 drug-related compounds, with 87 prototype entities mainly identified in rat plasma. NBDC significantly attenuated METH-induced behavioural anomalies and modulated neurotransmitter levels, notably increasing brain DA and serotonin (5-HT) content with concomitant upregulation of D1 dopamine receptor (DRD1) and 5-HT1A receptor (5-HT1AR) expression, ameliorating hippocampal pathology. Metabolomic analysis identified histamine receptor as a potential target and revealed the involvement of NBDC in metabolic pathways associated with cocaine addiction, amphetamine abuse and Parkinson's disease. Conclusively, NBDC presents a promising therapeutic agent for mitigating MA addiction through a synergistic interplay of multiple constituents, pharmacological targets and metabolic pathways.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631106","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":"Methamphetamine-related working memory difficulties underpinned by reduced frontoparietal responses","authors":"Robert J. Roy,&nbsp;Muhammad A. Parvaz,&nbsp;Ken T. Wakabayashi,&nbsp;Robert J. R. Blair,&nbsp;Nicholas A. Hubbard","doi":"10.1111/adb.13444","DOIUrl":"https://doi.org/10.1111/adb.13444","url":null,"abstract":"<p>Working memory difficulties are common, debilitating, and may pose barriers to recovery for people who use methamphetamine. Yet, little is known regarding the neural dysfunctions accompanying these difficulties. Here, we acquired cross-sectional, functional magnetic resonance imaging while people with problematic methamphetamine-use experience (MA⁺, <i>n =</i> 65) and people without methamphetamine-use experience (MA⁻, <i>n =</i> 44) performed a parametric <i>n</i>-back task (0-back through 2-back). Performance on tasks administered outside of the scanner, together with <i>n</i>-back performance, afforded to determine a latent dimension of participants' working memory ability. Behavioural results indicated that MA⁺ participants exhibited lower scores on this dimension compared to MA⁻ participants (<i>d =</i> −1.39, <i>p</i> &lt; .001). Whole-brain imaging results also revealed that MA⁺ participants exhibited alterations in load-induced responses predominantly in frontoparietal and default-mode areas. Specifically, while the MA⁻ group exhibited monotonic activation increases within frontoparietal areas and monotonic decreases within default-mode areas from 0-back to 2-back, MA⁺ participants showed a relative attenuation of these load-induced activation patterns (<i>d</i> = −1.55, <i>p</i> &lt; .001). Moreover, increased activations in frontoparietal areas from 0- to 2-back were related to greater working memory ability among MA⁺ participants (<i>r</i> = .560, <i>p</i> = .004). No such effects were observed for default-mode areas. In sum, reductions in working memory ability were observed alongside load-induced dysfunctions in frontoparietal and default-mode areas for people with problematic methamphetamine-use experience. Among them, load-induced activations within frontoparietal areas were found to have a strong and specific relationship to individual differences in working memory ability, indicating a putative neural signature of the working memory difficulties associated with chronic methamphetamine use.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443445","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":"Comment on: ‘Sex differences in neural networks recruited by frontloaded binge alcohol drinking’","authors":"Jiayue Xu,&nbsp;Hua Zhao,&nbsp;Ying Wang","doi":"10.1111/adb.70002","DOIUrl":"https://doi.org/10.1111/adb.70002","url":null,"abstract":"&lt;p&gt;We read the published article about ‘Sex differences in neural networks recruited by frontloaded binge alcohol drinking’ by Ardinger et al.,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and carried on the in-depth analysis of its content. Using whole brain imaging techniques and graph theory analysis methods, this paper revealed gender differences in alcohol preloading behaviour in brain network activity, providing new insights into gender differences in alcohol use disorders. However, we think there is still room for improvement in the following aspects.&lt;/p&gt;&lt;p&gt;First of all, the article focused on alcohol intake, and more behavioural indicators, such as anxiety, depression, and addictive behaviours, can be considered to more comprehensively assess the impact of alcohol preloading behaviours. Physiological indicators such as cortisol levels can also be considered to explore the relationship between alcohol preloading behaviour and stress response.&lt;/p&gt;&lt;p&gt;Second, C57BL/6J mice are commonly used animal models for alcohol research, but their alcohol intake behaviour may be different from that of humans. Other alcohol preference animal models, such as DBA/2 mice, could be considered to enhance the generalizability of the findings. At the same time, the DID paradigm can simulate human alcohol preloading behaviour, but other behavioural paradigms, such as operant conditioning, can be considered for more fine-grained control of alcohol intake behaviour.&lt;/p&gt;&lt;p&gt;Third, the paper clustered brain regions into modules based only on connection strength, and further analysis of the function of each module can be considered, such as using functional connection analysis or functional magnetic resonance imaging, to reveal the role of different modules in alcohol preloading behaviour. Dynamic network analysis methods, such as time series network analysis, can also be considered to explore the effect of alcohol preloading behaviour on dynamic changes in brain functional connectivity.&lt;/p&gt;&lt;p&gt;Then, for the results presentation part, we recommend more advanced network visualization tools, such as Gephi or Cytoscape, to more clearly demonstrate brain network structure and functional connectivity. Multivariate statistical analysis or machine learning algorithms can also be used to analyse the data more deeply.&lt;/p&gt;&lt;p&gt;Finally, the article mainly described the relationship between alcohol preloading behaviour and brain network activity, but lacks causal inference. Brain stimulation techniques or gene knockout techniques can be considered to explore the role of specific brain regions or neurotransmitter systems in alcohol preloading behaviour. The relationship between alcohol preloading behaviour and alcohol use disorder and its potential targets for intervention can also be explored.&lt;/p&gt;&lt;p&gt;We believe that with the above improvements, the article will shed more light on the neural mechanisms of alcohol preloading behaviour and provide new perspectives for understanding gender differences in alc","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438989","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":"Development of an evaluation method for addictive compounds based on electrical activity of human iPS cell-derived dopaminergic neurons using microelectrode array","authors":"Yuto Ishibashi,&nbsp;Nami Nagafuku,&nbsp;Shingo Kimura,&nbsp;Xiaobo Han,&nbsp;Ikuro Suzuki","doi":"10.1111/adb.13443","DOIUrl":"10.1111/adb.13443","url":null,"abstract":"<p>Addiction is known to occur through the consumption of substances such as pharmaceuticals, illicit drugs, food, alcohol and tobacco. These addictions can be viewed as drug addiction, resulting from the ingestion of chemical substances contained in them. Multiple neural networks, including the reward system, anti-reward/stress system and central immune system in the brain, are believed to be involved in the onset of drug addiction. Although various compound evaluations using microelectrode array (MEA) as an in vitro testing methods to evaluate neural activities have been conducted, methods for assessing addiction have not been established. In this study, we aimed to develop an in vitro method for assessing the addiction of compounds, as an alternative to animal experiments, using human iPS cell-derived dopaminergic neurons with MEA measurements. MEA data before and after chronic exposure revealed specific changes in addictive compounds compared to non-addictive compounds, demonstrating the ability to estimate addiction of compound. Additionally, conducting gene expression analysis on cultured samples after the tests revealed changes in the expression levels of various receptors (nicotine, dopamine and GABA) due to chronic administration of addictive compounds, suggesting the potential interpretation of these expression changes as addiction-like responses in MEA measurements. The addiction assessment method using MEA measurements in human iPS cell-derived dopaminergic neurons conducted in this study proves effective in evaluating addiction of compounds on human neural networks.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394506","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 glucagon-like peptide-1 and other endocrine responses to alcohol ingestion in women with versus without metabolic surgery","authors":"Mariel Molina-Castro,&nbsp;Neda Seyedsadjadi,&nbsp;Danisa Nieto,&nbsp;Lorenzo Leggio,&nbsp;Blair Rowitz,&nbsp;Marta Yanina Pepino","doi":"10.1111/adb.13441","DOIUrl":"10.1111/adb.13441","url":null,"abstract":"<p>Glucagon-like peptide-1 (GLP-1)-based therapies, effective in treating obesity and type 2 diabetes, hold potential for reducing alcohol-seeking behaviour. However, the understanding of how alcohol consumption affects endogenous GLP-1 responses—important for understanding GLP-1-based therapies' potential in addressing alcohol misuse—is limited, given the absence of placebo-controlled studies examining these effects. This study aimed to determine the acute effects of alcohol ingestion on GLP-1 and other peptides and evaluate whether metabolic surgery, which increases GLP-1 responses, blood alcohol concentrations (BAC) and alcohol misuse risk, influences this effect. Additionally, we assessed the acute effects of alcohol on plasma glucose and insulin concentrations. Using a placebo-controlled crossover study, we examined hormonal and glucose responses after oral alcohol consumption (0.5 g/kg of fat-free mass) versus placebo drinks in 18 women who underwent metabolic surgery &lt;5 years ago and in 14 non-operated controls (equivalent in age, body mass index [BMI], race and alcohol consumption patterns). Women had a mean (SD) age of 41 (10) years and a BMI of 33 (5) kg/m². Compared with the control group, the surgery group exhibited a higher peak BAC (0.99 [0.20] g/L vs. 0.75 [0.16] g/L; <i>P</i> &lt; 0.005). Alcohol decreased GLP-1 by 34% (95% CI, 16%–52%) in both groups and decreased ghrelin more in the control (27%) than in the surgery group (13%). Alcohol modestly decreased plasma glucose and transiently increased insulin secretion in both groups (<i>P</i> &lt; 0.05). However, alcohol lowered blood glucose concentrations to the hypoglycaemic range in 28% of the women in the surgery group versus none in the control group. These findings provide compelling evidence that acute alcohol consumption decreases GLP-1, a satiation signal, elucidating alcohol's ‘apéritif’ effect. This study also highlights the potential increase in alcohol-related hypoglycaemic effects after metabolic surgery.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394508","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":"Orbitofrontal cortex to dorsal striatum circuit is critical for incubation of oxycodone craving after forced abstinence","authors":"Hongyu Lin,&nbsp;Adedayo Olaniran,&nbsp;Xiang Luo,&nbsp;Jessica Strauch,&nbsp;Megan A. M. Burke,&nbsp;Chloe L. Matheson,&nbsp;Xuan Li","doi":"10.1111/adb.13440","DOIUrl":"10.1111/adb.13440","url":null,"abstract":"<p>Relapse is a major challenge in treating opioid addiction, including oxycodone. During abstinence, oxycodone seeking progressively increases, a phenomenon termed incubation of oxycodone craving. We previously demonstrated a causal role of orbitofrontal cortex (OFC) in this incubation. Here, we studied the interaction between glutamatergic projections from OFC and dopamine 1-family receptor (D1R) signaling in dorsal striatum (DS) in this incubation in male rats. We first examined the causal role of D1R signalling in DS in incubated oxycodone seeking. Next, we combined fluorescence-conjugated cholera toxin subunit B (CTb-555, a retrograde tracer) with Fos (a neuronal activity marker) to assess whether the activation of OFC→DS projections was associated with incubated oxycodone seeking. We then used a pharmacological asymmetrical disconnection procedure to examine the role of the interaction between projections from OFC and D1R signalling in DS in incubated oxycodone seeking. We also tested the effect of unilateral pharmacological inactivation of OFC or unilateral D1R blockade of DS on incubated oxycodone seeking. Finally, we assessed whether contralateral disconnection of OFC→DS projections impacted non-incubated oxycodone seeking on abstinence day 1. We found that D1R blockade in DS decreased incubated oxycodone seeking and OFC→DS projections were activated during incubated oxycodone seeking. Moreover, anatomical disconnection of OFC→DS projections, but not unilateral inactivation of OFC or unilateral D1R blockade in DS, decreased incubated oxycodone seeking. Lastly, contralateral disconnection of OFC→DS projections had no effect on oxycodone seeking on abstinence day 1. Together, these results demonstrated a causal role of OFC→DS projections in incubation of oxycodone craving.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394507","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}