Genes Brain and Behavior最新文献

{"title":"Patterns of ethanol intake in male rats with partial dopamine transporter deficiency","authors":"L. B. Kuiper,&nbsp;J. B. Roberts,&nbsp;P. M. Estave,&nbsp;D. Leo,&nbsp;R. R. Gainetdinov,&nbsp;S. R. Jones","doi":"10.1111/gbb.12847","DOIUrl":"10.1111/gbb.12847","url":null,"abstract":"<p>Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/−) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/− rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/− rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/− males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9824706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of early adversity and education on genetic and brain morphological predictors of cognitive ability","authors":"Emma Corley,&nbsp;Laura Fahey,&nbsp;Joan Fitzgerald,&nbsp;Laurena Holleran,&nbsp;Esther Walton,&nbsp;Derek W. Morris,&nbsp;Gary Donohoe","doi":"10.1111/gbb.12850","DOIUrl":"10.1111/gbb.12850","url":null,"abstract":"<p>Cognitive ability is a strong predictor of occupational achievement, quality of life and physical health. While variation in cognition is strongly heritable and has been robustly associated with early environment and brain morphology, little is known about how these factors combine and interact to explain this variation in cognition. To address this, we modelled the relationship between common genetic variation, grey matter volume, early life adversity and education and cognitive ability in a UK Biobank sample of <i>N</i> = 5237 individuals using structural equation modelling. We tested the hypotheses that total grey matter volume would mediate the association between genetic variation and cognitive ability, and that early life adversity and educational attainment would moderate this relationship. Common genetic variation, grey matter volume and early life adversity were each significant predictors in the model, explaining ~15% of variation in cognitive ability. Contrary to our hypothesis, grey matter volume did not mediate the relation between genetic variation and cognition performance. Neither did early life adversity or educational attainment moderate this relation, although educational attainment was observed to moderate the relationship between grey matter volume and cognitive performance. We interpret these findings in terms of the modest explanatory value of currently estimated polygenic scores accounting for variation in cognitive performance (~5%), making potential mediating and moderating variables difficult to confirm.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The collaborative study on the genetics of alcoholism: Genetics","authors":"Emma C. Johnson,&nbsp;Jessica E. Salvatore,&nbsp;Dongbing Lai,&nbsp;Alison K. Merikangas,&nbsp;John I. Nurnberger,&nbsp;Jay A. Tischfield,&nbsp;Xiaoling Xuei,&nbsp;Chella Kamarajan,&nbsp;Leah Wetherill,&nbsp;COGA Collaborators,&nbsp;John P. Rice,&nbsp;John R. Kramer,&nbsp;Samuel Kuperman,&nbsp;Tatiana Foroud,&nbsp;Paul A. Slesinger,&nbsp;Alison M. Goate,&nbsp;Bernice Porjesz,&nbsp;Danielle M. Dick,&nbsp;Howard J. Edenberg,&nbsp;Arpana Agrawal","doi":"10.1111/gbb.12856","DOIUrl":"10.1111/gbb.12856","url":null,"abstract":"<p>This review describes the genetic approaches and results from the family-based Collaborative Study on the Genetics of Alcoholism (COGA). COGA was designed during the linkage era to identify genes affecting the risk for alcohol use disorder (AUD) and related problems, and was among the first AUD-focused studies to subsequently adopt a genome-wide association (GWAS) approach. COGA's family-based structure, multimodal assessment with gold-standard clinical and neurophysiological data, and the availability of prospective longitudinal phenotyping continues to provide insights into the etiology of AUD and related disorders. These include investigations of genetic risk and trajectories of substance use and use disorders, phenome-wide association studies of loci of interest, and investigations of pleiotropy, social genomics, genetic nurture, and within-family comparisons. COGA is one of the few AUD genetics projects that includes a substantial number of participants of African ancestry. The sharing of data and biospecimens has been a cornerstone of the COGA project, and COGA is a key contributor to large-scale GWAS consortia. COGA's wealth of publicly available genetic and extensive phenotyping data continues to provide a unique and adaptable resource for our understanding of the genetic etiology of AUD and related traits.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e9/f4/GBB-22-e12856.PMC10550788.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9843742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapamycin improves social and stereotypic behavior abnormalities induced by pre-mitotic neuronal subset specific Pten deletion","authors":"David A. Narvaiz,&nbsp;Suzanne O. Nolan,&nbsp;Gregory D. Smith,&nbsp;Andrew J. Holley,&nbsp;Conner D. Reynolds,&nbsp;Katherine J. Blandin,&nbsp;Phuoc H. Nguyen,&nbsp;Doan L. K. Tran,&nbsp;Joaquin N. Lugo","doi":"10.1111/gbb.12854","DOIUrl":"10.1111/gbb.12854","url":null,"abstract":"<p>The mechanistic target of rapamycin (mTOR) pathway is a signaling system integral to neural growth and migration. In both patients and rodent models, mutations to the phosphatase and tensin homolog gene (<i>PTEN</i>) on chromosome 10 results in hyperactivation of the mTOR pathway, as well as seizures, intellectual disabilities and autistic behaviors. Rapamycin, an inhibitor of mTOR, can reverse the epileptic phenotype of neural subset specific <i>Pten</i> knockout (NS-<i>Pten</i> KO) mice, but its impact on behavior is not known. To determine the behavioral effects of rapamycin, male and female NS-<i>Pten</i> KO and wildtype (WT) mice were assigned as controls or administered 10 mg/kg of rapamycin for 2 weeks followed by behavioral testing. Rapamycin improved social behavior in both genotypes and stereotypic behaviors in NS-<i>Pten</i> KO mice. Rapamycin treatment resulted in a reduction of several measures of activity in the open field test in both genotypes. Rapamycin did not reverse the reduced anxiety behavior in KO mice. These data show the potential clinical use of mTOR inhibitors by showing its administration can reduce the production of autistic-like behaviors in NS-<i>Pten</i> KO mice.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12854","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extensive characterization of a Williams syndrome murine model shows Gtf2ird1-mediated rescue of select sensorimotor tasks, but no effect on enhanced social behavior","authors":"Kayla R. Nygaard,&nbsp;Susan E. Maloney,&nbsp;Raylynn G. Swift,&nbsp;Katherine B. McCullough,&nbsp;Rachael E. Wagner,&nbsp;Stuart B. Fass,&nbsp;Krassimira Garbett,&nbsp;Karoly Mirnics,&nbsp;Jeremy Veenstra-VanderWeele,&nbsp;Joseph D. Dougherty","doi":"10.1111/gbb.12853","DOIUrl":"10.1111/gbb.12853","url":null,"abstract":"<p>Williams syndrome is a rare neurodevelopmental disorder exhibiting cognitive and behavioral abnormalities, including increased social motivation, risk of anxiety and specific phobias along with perturbed motor function. Williams syndrome is caused by a microdeletion of 26–28 genes on chromosome 7, including <i>GTF2IRD1</i>, which encodes a transcription factor suggested to play a role in the behavioral profile of Williams syndrome. Duplications of the full region also lead to frequent autism diagnosis, social phobias and language delay. Thus, genes in the region appear to regulate social motivation in a dose-sensitive manner. A “complete deletion” mouse, heterozygously eliminating the syntenic Williams syndrome region, has been deeply characterized for cardiac phenotypes, but direct measures of social motivation have not been assessed. Furthermore, the role of <i>Gtf2ird1</i> in these behaviors has not been addressed in a relevant genetic context. Here, we have generated a mouse overexpressing <i>Gtf2ird1</i>, which can be used both to model duplication of this gene alone and to rescue <i>Gtf2ird1</i> expression in the complete deletion mice. Using a comprehensive behavioral pipeline and direct measures of social motivation, we provide evidence that the Williams syndrome critical region regulates social motivation along with motor and anxiety phenotypes, but that <i>Gtf2ird1</i> complementation is not sufficient to rescue most of these traits, and duplication does not decrease social motivation. However, <i>Gtf2ird1</i> complementation does rescue light-aversive behavior and performance on select sensorimotor tasks, perhaps indicating a role for this gene in sensory processing or integration.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12853","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and environmental influences on one-trial conditioned context aversion in mice","authors":"Çınar Furkan İlhan,&nbsp;Gonzalo P. Urcelay,&nbsp;Sezen Kışlal","doi":"10.1111/gbb.12857","DOIUrl":"10.1111/gbb.12857","url":null,"abstract":"<p>Anticipatory nausea (AN) is caused by an association between contextual cues and the experience of nausea (the side effects of chemotherapy or radiation treatment) and it develops predominantly in female patients undergoing chemotherapy. Preclinical studies in rodents show that the administration of an illness-inducing agent in the presence of novel contextual cues can cause conditioned context aversion (CCA) and this has been proposed to model AN. The literature also suggests that brief pre-exposure to a novel context prior to shock delivery is critical in the development of contextual fear conditioning in rodents (a phenomenon known as Immediate Shock Deficit), but this has not been assessed in CCA. The aim of present study was to develop a CCA paradigm to assess this in outbred (CD1) and inbred (C57BL/6J) mice and evaluate potential sex differences. The results revealed that a single conditioning trial in which a distinctive context was paired with LiCl-induced illness was sufficient to elicit a conditioned response in both female and male CD1 outbred mice, but not in C57BL/6J inbred mice. In addition, CCA was facilitated when animals had prior experience with the context. Finally, outbred female mice showed longer and more robust retention of CCA than male mice, which parallels clinical findings. The results indicate the importance of using CD1 outbred mice as an animal model of AN as well as examining sex differences in the CCA paradigm. Similar findings in humans encourage the future use of this novel CCA preclinical mouse model.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ed/a4/GBB-22-e12857.PMC10393421.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9915041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous allelic variant in deafness–blindness gene Ush1g resulting in an expanded phenotype","authors":"Vladimir Vartanian,&nbsp;Jocelyn F. Krey,&nbsp;Paroma Chatterjee,&nbsp;Allison Curtis,&nbsp;Makayla Six,&nbsp;Sean P. M. Rice,&nbsp;Sherri M. Jones,&nbsp;Harini Sampath,&nbsp;Charles N. Allen,&nbsp;Renee C. Ryals,&nbsp;R. Stephen Lloyd,&nbsp;Peter G. Barr-Gillespie","doi":"10.1111/gbb.12849","DOIUrl":"10.1111/gbb.12849","url":null,"abstract":"Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target‐specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards‐walking behavior in open‐field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1gbw/bw null mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner‐ear hair‐cell function, including a complete lack of auditory brainstem responses and vestibular‐evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell's kinocilial links. Consistent with other Usher type 1 models, Ush1gbw/bw mice had no substantial retinal degeneration compared with Ush1gbw/+ controls. In contrast to previously described Ush1g alleles, this new allele provides the first knockout model for this gene.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/a6/GBB-22-e12849.PMC10393423.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin ameliorates sleep–wake disturbances and autism-like behaviors in the Ctnnd2 knock out mouse model of autism spectrum disorders","authors":"Man Xu,&nbsp;Luyi Wang,&nbsp;Yan Wang,&nbsp;Jing Deng,&nbsp;Xiaoya Wang,&nbsp;Feifei Wang,&nbsp;Sen Pan,&nbsp;Yu Zhao,&nbsp;Ailing Liao,&nbsp;Xiaoqing Wang,&nbsp;Di Chen,&nbsp;Jingjing Shen,&nbsp;Feng Yang,&nbsp;Yingbo Li,&nbsp;Shali Wang","doi":"10.1111/gbb.12852","DOIUrl":"10.1111/gbb.12852","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical patterns of social interaction and communication, as well as restrictive and repetitive behaviors. In addition, patients with ASD often presents with sleep disturbances. Delta (δ) catenin protein 2 (<i>CTNND2</i>) encodes δ-catenin protein, a neuron-specific catenin implicated in many complex neuropsychiatric diseases. Our previous study demonstrated that the deletion of <i>Ctnnd2</i> in mice led to autism-like behaviors. However, to our knowledge, no study has investigated the effects of <i>Ctnnd2</i> deletion on sleep in mice. In this study, we investigated whether the knockout (KO) of exon 2 of the <i>Ctnnd2</i> gene could induce sleep–wake disorders in mice and identified the effects of oral melatonin (MT) supplementation on <i>Ctnnd2</i> KO mice. Our results demonstrated that the <i>Ctnnd2</i> KO mice exhibited ASD-like behaviors and sleep–wake disorders that were partially attenuated by MT supplementation. Overall, our current study is the first to identify that knockdown of <i>Ctnnd2</i> gene could induce sleep–wake disorders in mice and suggests that treatment of sleep–wake disturbances by MT may benefit to autism-like behaviors causing by <i>Ctnnd2</i> gene deletion.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/c8/GBB-22-e12852.PMC10393424.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9920408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testing associations between human anxiety and genes previously implicated by mouse anxiety models","authors":"Maizy S. Brasher,&nbsp;Travis J. Mize,&nbsp;Aimee L. Thomas,&nbsp;Charles A. Hoeffer,&nbsp;Marissa A. Ehringer,&nbsp;Luke M. Evans","doi":"10.1111/gbb.12851","DOIUrl":"10.1111/gbb.12851","url":null,"abstract":"<p>Anxiety disorders are common and can be debilitating, with effective treatments remaining hampered by an incomplete understanding of the underlying genetic etiology. Improvements have been made in understanding the genetic influences on mouse behavioral models of anxiety, yet it is unclear the extent to which genes identified in these experimental systems contribute to genetic variation in human anxiety phenotypes. Leveraging new and existing large-scale human genome-wide association studies, we tested whether sets of genes previously identified in mouse anxiety-like behavior studies contribute to a range of human anxiety disorders. When tested as individual genes, 13 mouse-identified genes were associated with human anxiety phenotypes, suggesting an overlap of individual genes contributing to both mouse models of anxiety-like behaviors and human anxiety traits. When genes were tested as sets, we did identify 14 significant associations between mouse gene sets and human anxiety, but the majority of gene sets showed no significant association with human anxiety phenotypes. These few significant associations indicate a need to identify and develop more translatable mouse models by identifying sets of genes that “match” between model systems and specific human phenotypes of interest. We suggest that continuing to develop improved behavioral paradigms and finer-scale experimental data, for instance from individual neuronal subtypes or cell-type-specific expression data, is likely to improve our understanding of the genetic etiology and underlying functional changes in anxiety disorders.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12851","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9924794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice","authors":"Thi Dong Binh Tran,&nbsp;Christian Monroy Hernandez,&nbsp;Hoan Nguyen,&nbsp;Susan Wright,&nbsp;Center for Systems Neurogenetics of Addiction,&nbsp;Lisa M. Tarantino,&nbsp;Elissa J. Chesler,&nbsp;George M. Weinstock,&nbsp;Yanjiao Zhou,&nbsp;Jason A. Bubier","doi":"10.1111/gbb.12845","DOIUrl":"10.1111/gbb.12845","url":null,"abstract":"<p>The gut-brain axis is increasingly recognized as an important pathway involved in cocaine use disorder. Microbial products of the murine gut have been shown to affect striatal gene expression, and depletion of the microbiome by antibiotic treatment alters cocaine-induced behavioral sensitization in C57BL/6J male mice. Some reports suggest that cocaine-induced behavioral sensitization is correlated with drug self-administration behavior in mice. Here, we profile the composition of the naïve microbiome and its response to cocaine sensitization in two collaborative cross (CC) strains. These strains display extremely divergent behavioral responses to cocaine sensitization. A high-responding strain, CC004/TauUncJ (CC04), has a gut microbiome that contains a greater amount of <i>Lactobacillus</i> than the cocaine-nonresponsive strain CC041/TauUncJ (CC41). The gut microbiome of CC41 is characterized by an abundance of <i>Eisenbergella</i>, <i>Robinsonella</i> and <i>Ruminococcus.</i> In response to cocaine, CC04 has an increased <i>Barnsiella</i> population, while the gut microbiome of CC41 displays no significant changes. PICRUSt functional analysis of the functional potential of the gut microbiome in CC04 shows a significant number of potential gut-brain modules altered after exposure to cocaine, specifically those encoding for tryptophan synthesis, glutamine metabolism, and menaquinone synthesis (vitamin K2). Depletion of the microbiome by antibiotic treatment revealed an altered cocaine-sensitization response following antibiotics in female CC04 mice. Depleting the microbiome by antibiotic treatment in males revealed increased infusions for CC04 during a cocaine intravenous self-administration dose–response curve. Together these data suggest that genetic differences in cocaine-related behaviors may involve the microbiome.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/2b/GBB-22-e12845.PMC10242200.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9772323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}