ArticleNeuroscience2014
Understanding the addiction cycle: a complex biology with distinct contributions of genotype vs. sex at each stage.
Article in Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Not just neurons: glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.Frontiers in neuroendocrinology · 2026Review
- Stress and gonadal steroid influences on alcohol drinking and withdrawal, with focus on animal models in females.Frontiers in neuroendocrinology · 2023Review
- Sex Differences in the Brain Transcriptome Related to Alcohol Effects and Alcohol Use Disorder.Biological psychiatry · 2022Review
- Polymorphism of Proteasomal Genes Can Be a Risk Factor for Systemic Autoimmune Diseases in Children.Journal of pediatric genetics · 2021Article
- Systems genetics analysis of the LXS recombinant inbred mouse strains:Genetic and molecular insights into acute ethanol tolerance.PloS one · 2020Article
- Affective Behavior in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant Mice during Long-Term Alcohol Abstinence.Alcoholism, clinical and experimental research · 2019Article
- Gender-Specific Effects of Selection for Drinking in the Dark on the Network Roles of Coding and Noncoding RNAs.Alcoholism, clinical and experimental research · 2018Article
- Binge Ethanol Drinking Produces Sexually Divergent and Distinct Changes in Nucleus Accumbens Signaling Cascades and Pathways in Adult C57BL/6J Mice.Frontiers in genetics · 2018Article
- Sex Differences in Neurotoxicogenetics.Frontiers in genetics · 2018Review
- Stable Histone Methylation Changes at Proteoglycan Network Genes Following Ethanol Exposure.Frontiers in genetics · 2018Article
- Peripheral immune factors are elevated in women with current or recent alcohol dependence and associated with altered mood and memory.Drug and alcohol dependence · 2017Article
- Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence.Alcohol (Fayetteville, N.Y.) · 2017Article
- The Role of NFkB in Drug Addiction: Beyond Inflammation.Alcohol and alcoholism (Oxford, Oxfordshire) · 2017Review
- Binge Eating Disorder (BED) in Relation to Addictive Behaviors and Personality Risk Factors.Frontiers in psychology · 2017Article
- Astrocyte Dysfunction Induced by Alcohol in Females but Not Males.Brain pathology (Zurich, Switzerland) · 2016Article
- Functional regulation of PI3K-associated signaling in the accumbens by binge alcohol drinking in male but not female mice.Neuropharmacology · 2016Article
- Sex Differences in Animal Models: Focus on Addiction.Pharmacological reviews · 2016Review
- Transitioning from First Drug Use to Dependence Onset: Illustration of a Multiparametric Approach for Comparative Epidemiology.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Females uniquely vulnerable to alcohol-induced neurotoxicity show altered glucocorticoid signaling.Brain research · 2015Article
- A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy.Neurotoxicology and teratologyArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ethanol abuse can lead to addiction, brain damage and premature death. The cycle of alcohol addiction has been described as a composite consisting of three stages: intoxication, withdrawal and craving/abstinence. There is evidence for contributions of both genotype and sex to alcoholism, but an understanding of the biological underpinnings is limited. Utilizing both sexes of genetic animal models with highly divergent alcohol withdrawal severity, Withdrawal Seizure-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) mice, the distinct contributions of genotype/phenotype and of sex during addiction stages on neuroadaptation were characterized. Transcriptional profiling was performed to identify expression changes as a consequence of chronic intoxication in the medial prefrontal cortex. Significant expression differences were identified on a single platform and tracked over a behaviorally relevant time course that covered each stage of alcohol addiction; i.e., after chronic intoxication, during peak withdrawal, and after a defined period of abstinence. Females were more sensitive to ethanol with higher fold expression differences. Bioinformatics showed a strong effect of sex on the data structure of expression profiles during chronic intoxication and at peak withdrawal irrespective of genetic background. However, during abstinence, differences were observed instead between the lines/phenotypes irrespective of sex. Confirmation of identified pathways showed distinct inflammatory signaling following intoxication at peak withdrawal, with a pro-inflammatory phenotype in females but overall suppression of immune signaling in males. Combined, these results suggest that each stage of the addiction cycle is influenced differentially by sex vs. genetic background and support the development of stage- and sex-specific therapies for alcohol withdrawal and the maintenance of sobriety.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.