Genes Brain and Behavior最新文献

{"title":"Extracellular vesicles from cerebrospinal fluid revealed changes in miR-19a-3p and miR-4516 expression in Slovene male suicides","authors":"Iris Šalamon Arčan,&nbsp;Mojca Katrašnik,&nbsp;Katarina Kouter,&nbsp;Tomaž Zupanc,&nbsp;Alja Videtič Paska","doi":"10.1111/gbb.12868","DOIUrl":"10.1111/gbb.12868","url":null,"abstract":"<p>Suicide is an important public-health concern, with more than 700,000 people dying by suicide yearly. It is a multifactorial phenomenon, shaped by the effects of sociodemographic, environmental and biological factors. The latter two factors can be linked through epigenetic studies, which examine differences in gene expression that are not due to changes in the DNA sequence itself. Epigenetic mechanisms include micro RNAs (miRNAs), which have a direct effect on already translated mRNA, leading to either decay or translational repression of the target mRNA. MiRNA molecules have been identified as cargo of extracellular vesicles (EVs) used by cells for long-distance communication, and pathophysiological changes in miRNA in brain cells may be reflected in cerebrospinal fluid (CSF) vesicles. In this study we investigated the presence and differential expression of selected miRNAs in EVs from the CSF of male suicide completers and controls. Western blot and nanoparticle tracking analyses confirmed the presence of small and medium sized EVs. Of the miRNA analyzed (miR-16-5p, miR-19a-3p, miR-34c-5p, miR-17-5p, miR-4286, miR-26b-5p, miR-381-3p, and miR-4516) miR-19a-3p and miR-4516 reached statistical significance with <i>p</i>-values of 0.0408 and 0.0168, respectively. Mir-4516 and miRNA-19a-3p have been previously studied in suicide, and target <i>SLC6A4</i> and <i>TNF-α</i> expression, correspondingly. Approximately 70% of known miRNAs are expressed in the central nervous system, and therefore represent an important biomarker potential. Investigating the cargo of CFS and blood EVs would further support the identification of miRNAs with clinical use potential.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12868","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123089","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: Overview","authors":"Arpana Agrawal,&nbsp;Sarah J. Brislin,&nbsp;Kathleen K. Bucholz,&nbsp;Danielle Dick,&nbsp;Ronald P. Hart,&nbsp;Emma C. Johnson,&nbsp;Jacquelyn Meyers,&nbsp;Jessica Salvatore,&nbsp;Paul Slesinger,&nbsp;COGA Collaborators,&nbsp;Laura Almasy,&nbsp;Tatiana Foroud,&nbsp;Alison Goate,&nbsp;Victor Hesselbrock,&nbsp;John Kramer,&nbsp;Samuel Kuperman,&nbsp;Alison K. Merikangas,&nbsp;John I. Nurnberger,&nbsp;Jay Tischfield,&nbsp;Howard J. Edenberg,&nbsp;Bernice Porjesz","doi":"10.1111/gbb.12864","DOIUrl":"10.1111/gbb.12864","url":null,"abstract":"<p>Alcohol use disorders (AUD) are commonly occurring, heritable and polygenic disorders with etiological origins in the brain and the environment. To outline the causes and consequences of alcohol-related milestones, including AUD, and their related psychiatric comorbidities, the Collaborative Study on the Genetics of Alcoholism (COGA) was launched in 1989 with a gene-brain-behavior framework. COGA is a family based, diverse (~25% self-identified African American, ~52% female) sample, including data on 17,878 individuals, ages 7–97 years, in 2246 families of which a proportion are densely affected for AUD. All participants responded to questionnaires (e.g., personality) and the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) which gathers information on psychiatric diagnoses, conditions and related behaviors (e.g., parental monitoring). In addition, 9871 individuals have brain function data from electroencephalogram (EEG) recordings while 12,009 individuals have been genotyped on genome-wide association study (GWAS) arrays. A series of functional genomics studies examine the specific cellular and molecular mechanisms underlying AUD. This overview provides the framework for the development of COGA as a scientific resource in the past three decades, with individual reviews providing in-depth descriptions of data on and discoveries from behavioral and clinical, brain function, genetic and functional genomics data. The value of COGA also resides in its data sharing policies, its efforts to communicate scientific findings to the broader community via a project website and its potential to nurture early career investigators and to generate independent research that has broadened the impact of gene-brain-behavior research into AUD.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/f4/GBB-22-e12864.PMC10550790.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41164915","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":"Collaborative study on the genetics of alcoholism: The strength of collaboration, team science, and longitudinal data","authors":"Marissa A. Ehringer","doi":"10.1111/gbb.12866","DOIUrl":"10.1111/gbb.12866","url":null,"abstract":"<p>This issue contains a series of articles describing the various resources, studies, results, and future directions for the collaborative study on the genetics of alcoholism (COGA). The collaborative and integrative approach initiated by this group ~30 years ago serves as an excellent example of the strength of team science. Individually, various aspects of COGA would be limited in their impact toward improved understanding of alcohol use disorder. Collectively, their wholistic approach which spans deep longitudinal phenotypic assessments in families to include the application of large-scale omics technologies and cell-culture based molecular studies has demonstrated the power of working together.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12866","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41162739","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":"A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/− rat model of genetic risk for psychiatric disorder","authors":"Simonas Griesius,&nbsp;Sophie Waldron,&nbsp;Katie A. Kamenish,&nbsp;Nick Cherbanich,&nbsp;Lawrence S. Wilkinson,&nbsp;Kerrie L. Thomas,&nbsp;Jeremy Hall,&nbsp;Jack R. Mellor,&nbsp;Dominic M. Dwyer,&nbsp;Emma S. J. Robinson","doi":"10.1111/gbb.12865","DOIUrl":"10.1111/gbb.12865","url":null,"abstract":"<p>Variations in the Dlg2 gene have been linked to increased risk for psychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability, bipolar disorder, attention deficit hyperactivity disorder, and pubertal disorders. Recent studies have reported disrupted brain circuit function and behaviour in models of Dlg2 knockout and haploinsufficiency. Specifically, deficits in hippocampal synaptic plasticity were found in heterozygous Dlg2+/− rats suggesting impacts on hippocampal dependent learning and cognitive flexibility. Here, we tested these predicted effects with a behavioural characterisation of the heterozygous Dlg2+/− rat model. Dlg2+/− rats exhibited a specific, mild impairment in reversal learning in a substrate deterministic bowl-digging reversal learning task. The performance of Dlg2+/− rats in other bowl digging task, visual discrimination and reversal, novel object preference, novel location preference, spontaneous alternation, modified progressive ratio, and novelty-suppressed feeding test were not impaired. These findings suggest that despite altered brain circuit function, behaviour across different domains is relatively intact in Dlg2+/− rats, with the deficits being specific to only one test of cognitive flexibility. The specific behavioural phenotype seen in this Dlg2+/− model may capture features of the clinical presentation associated with variation in the Dlg2 gene.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12865","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286215","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: Brain function","authors":"Jacquelyn L. Meyers,&nbsp;Sarah J. Brislin,&nbsp;Chella Kamarajan,&nbsp;Martin H. Plawecki,&nbsp;David Chorlian,&nbsp;Andrey Anohkin,&nbsp;Samuel Kuperman,&nbsp;Alison Merikangas,&nbsp;Gayathri Pandey,&nbsp;Sivan Kinreich,&nbsp;Ashwini Pandey,&nbsp;Howard J. Edenberg,&nbsp;Kathleen K. Bucholz,&nbsp;COGA Collaborators,&nbsp;Laura Almasy,&nbsp;Bernice Porjesz","doi":"10.1111/gbb.12862","DOIUrl":"10.1111/gbb.12862","url":null,"abstract":"<p>Alcohol use disorder (AUD) and related health conditions result from a complex interaction of genetic, neural and environmental factors, with differential impacts across the lifespan. From its inception, the Collaborative Study on the Genetics of Alcoholism (COGA) has focused on the importance of brain function as it relates to the risk and consequences of alcohol use and AUD, through the examination of noninvasively recorded brain electrical activity and neuropsychological tests. COGA's sophisticated neurophysiological and neuropsychological measures, together with rich longitudinal, multi-modal family data, have allowed us to disentangle brain-related risk and resilience factors from the consequences of prolonged and heavy alcohol use in the context of genomic and social-environmental influences over the lifespan. COGA has led the field in identifying genetic variation associated with brain functioning, which has advanced the understanding of how genomic risk affects AUD and related disorders. To date, the COGA study has amassed brain function data on over 9871 participants, 7837 with data at more than one time point, and with notable diversity in terms of age (from 7 to 97), gender (52% female), and self-reported race and ethnicity (28% Black, 9% Hispanic). These data are available to the research community through several mechanisms, including directly through the NIAAA, through dbGAP, and in collaboration with COGA investigators. In this review, we provide an overview of COGA's data collection methods and specific brain function measures assessed, and showcase the utility, significance, and contributions these data have made to our understanding of AUD and related disorders, highlighting COGA research findings.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12862","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10105392","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: Sample and clinical data","authors":"Danielle M. Dick,&nbsp;Emily Balcke,&nbsp;Vivia McCutcheon,&nbsp;Meredith Francis,&nbsp;Sally Kuo,&nbsp;Jessica Salvatore,&nbsp;Jacquelyn Meyers,&nbsp;Laura J. Bierut,&nbsp;Marc Schuckit,&nbsp;Victor Hesselbrock,&nbsp;Howard J. Edenberg,&nbsp;Bernice Porjesz,&nbsp;COGA Collaborators,&nbsp;Samuel Kuperman,&nbsp;John Kramer,&nbsp;Kathleen Bucholz","doi":"10.1111/gbb.12860","DOIUrl":"10.1111/gbb.12860","url":null,"abstract":"<p>The collaborative study on the genetics of alcoholism (COGA) is a multi-site, multidisciplinary project with the goal of identifying how genes are involved in alcohol use disorder and related outcomes, and characterizing how genetic risk unfolds across development and in conjunction with the environment and brain function. COGA is a multi-generational family-based study in which probands were recruited through alcohol treatment centers, along with a set of community comparison families. Nearly 18,000 individuals from &gt;2200 families have been assessed over a period of over 30 years with a rich phenotypic battery that includes semi-structured psychiatric interviews and questionnaire measures, along with DNA collection and electrophysiological data on a large subset. Participants range in age from 7 to 97, with many having longitudinal assessments, providing a valuable opportunity to study alcohol use and problems across the lifespan. Here we provide an overview of data collection methods for the COGA sample, and details about sample characteristics and comorbidity. We also review key research findings that have emerged from analyses of the COGA data. COGA data are available broadly to researchers, and we hope this overview will encourage further collaboration and use of these data to advance the field.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/38/GBB-22-e12860.PMC10550787.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997850","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":"Impaired erythropoietin-producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats","authors":"Yiqian Shao,&nbsp;Yaqi Cai,&nbsp;Tengfei Chen,&nbsp;Keke Hao,&nbsp;Binbin Luo,&nbsp;Xiujuan Wang,&nbsp;Weiyun Guo,&nbsp;Xi Su,&nbsp;Luxian Lv,&nbsp;Yongfeng Yang,&nbsp;Wenqiang Li","doi":"10.1111/gbb.12863","DOIUrl":"10.1111/gbb.12863","url":null,"abstract":"<p>An environmental risk factor for schizophrenia (SZ) is maternal infection, which exerts longstanding effects on the neurodevelopment of offspring. Accumulating evidence suggests that synaptic disturbances may contribute to the pathology of the disease, but the underlying molecular mechanisms remain poorly understood. Erythropoietin-producing hepatocellular B (EphB) receptor signaling plays an important role in synaptic plasticity by regulating the formation and maturation of dendritic spines and regulating excitatory neurotransmission. We examined whether EphB receptors and downstream associated proteins are susceptible to environmental risk factors implicated in the etiology of synaptic disturbances in SZ. Using an established rodent model, which closely imitates the characteristics of SZ, we observed the behavioral performance and synaptic structure of male offspring in adolescence and early adulthood. We then analyzed the expression of EphB receptors and associated proteins in the prefrontal cortex and hippocampus. Maternal immune activation offspring showed significantly progressive cognitive impairment and pre-pulse inhibition deficits together with an increase in the expression of EphB2 receptors and NMDA receptor subunits. We also found changes in EphB receptor downstream signaling, in particular, a decrease in phospho-cofilin levels which may explain the reduced dendritic spine density. Besides, we found that the AMPA glutamate, another glutamate ionic receptor associated with cofilin, decreased significantly in maternal immune activation offspring. Thus, alterations in EphB signaling induced by immune activation during pregnancy may underlie disruptions in synaptic plasticity and function in the prefrontal cortex and hippocampus associated with behavioral and cognitive impairment. These findings may provide insight into the mechanisms underlying SZ.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12863","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362692","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":"Developmental coordination disorder: What can we learn from RI mice using motor learning tasks and QTL analysis","authors":"Kamaldeep Gill,&nbsp;Jeffy Rajan Soundara Rajan,&nbsp;Eric Chow,&nbsp;David G. Ashbrook,&nbsp;Robert W. Williams,&nbsp;Jill G. Zwicker,&nbsp;Daniel Goldowitz","doi":"10.1111/gbb.12859","DOIUrl":"10.1111/gbb.12859","url":null,"abstract":"<p>Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder of unknown etiology that affects one in 20 children. There is an indication that DCD has an underlying genetic component due to its high heritability. Therefore, we explored the use of a recombinant inbred family of mice known as the BXD panel to understand the genetic basis of complex traits (i.e., motor learning) through identification of quantitative trait loci (QTLs). The overall aim of this study was to utilize the QTL approach to evaluate the genome-to-phenome correlation in BXD strains of mice in order to better understand the human presentation of DCD. Results of this current study confirm differences in motor learning in selected BXD strains and strains with altered cerebellar volume. Five strains – BXD15, BXD27, BXD28, BXD75, and BXD86 – exhibited the most DCD-like phenotype when compared with other BXD strains of interest. Results indicate that BXD15 and BXD75 struggled primarily with gross motor skills, BXD28 primarily had difficulties with fine motor skills, and BXD27 and BXD86 strains struggled with both fine and gross motor skills. The functional roles of genes within significant QTLs were assessed in relation to DCD-like behavior. Only <i>Rab3a</i> (Ras-related protein Rab-3A) emerged as a high likelihood candidate gene for the horizontal ladder rung task. This gene is associated with brain and skeletal muscle development, but lacked nonsynonymous polymorphisms. This study along with Gill et al. (same issue) is the first studies to specifically examine the genetic linkage of DCD using BXD strains of mice.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12859","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960199","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":"5. Collaborative Study on the Genetics of Alcoholism: Functional genomics","authors":"Isabel Gameiro-Ros,&nbsp;Dina Popova,&nbsp;Iya Prytkova,&nbsp;Zhiping P. Pang,&nbsp;Yunlong Liu,&nbsp;Danielle Dick,&nbsp;Kathleen K. Bucholz,&nbsp;Arpana Agrawal,&nbsp;Bernice Porjesz,&nbsp;Alison M. Goate,&nbsp;Xiaoling Xuei,&nbsp;Chella Kamarajan,&nbsp;COGA Collaborators,&nbsp;Jay A. Tischfield,&nbsp;Howard J. Edenberg,&nbsp;Paul A. Slesinger,&nbsp;Ronald P. Hart","doi":"10.1111/gbb.12855","DOIUrl":"10.1111/gbb.12855","url":null,"abstract":"<p>Alcohol Use Disorder is a complex genetic disorder, involving genetic, neural, and environmental factors, and their interactions. The Collaborative Study on the Genetics of Alcoholism (COGA) has been investigating these factors and identified putative alcohol use disorder risk genes through genome-wide association studies. In this review, we describe advances made by COGA in elucidating the functional changes induced by alcohol use disorder risk genes using multimodal approaches with human cell lines and brain tissue. These studies involve investigating gene regulation in lymphoblastoid cells from COGA participants and in post-mortem brain tissues. High throughput reporter assays are being used to identify single nucleotide polymorphisms in which alternate alleles differ in driving gene expression. Specific single nucleotide polymorphisms (both coding or noncoding) have been modeled using induced pluripotent stem cells derived from COGA participants to evaluate the effects of genetic variants on transcriptomics, neuronal excitability, synaptic physiology, and the response to ethanol in human neurons from individuals with and without alcohol use disorder. We provide a perspective on future studies, such as using polygenic risk scores and populations of induced pluripotent stem cell-derived neurons to identify signaling pathways related with responses to alcohol. Starting with genes or loci associated with alcohol use disorder, COGA has demonstrated that integration of multimodal data within COGA participants and functional studies can reveal mechanisms linking genomic variants with alcohol use disorder, and potential targets for future treatments.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/5a/GBB-22-e12855.PMC10550792.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042569","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":"Partner-seeking and limbic dopamine system are enhanced following social loss in male prairie voles (Microtus ochrogaster)","authors":"Erika M. Vitale,&nbsp;Adrianna Kirckof,&nbsp;Adam S. Smith","doi":"10.1111/gbb.12861","DOIUrl":"10.1111/gbb.12861","url":null,"abstract":"<p>Death of a loved one is recognized as one of life's greatest stresses, and 10%–20% of bereaved individuals will experience a complicated or prolonged grieving period that is characterized by intense yearning for the deceased. The monogamous prairie vole (<i>Microtus ochrogaster</i>) is a rodent species that forms pair bonds between breeding partners and has been used to study the neurobiology of social behaviors and isolation. Male prairie voles do not display distress after isolation from a familiar, same-sex conspecific; however, separation from a bonded female partner increases emotional, stress-related, and proximity-seeking behaviors. Here, we tested the investigatory response of male voles to partner odor during a period of social loss. We found that males who lost their partner spent significantly more time investigating partner odor but not non-partner social odor or food odor. Bachelor males and males in intact pairings did not respond uniquely to any odor. Furthermore, we examined dopamine (DA) receptor mRNA expression in the anterior insula cortex (aIC), nucleus accumbens (NAc), and anterior cingulate (ACC), regions with higher activation in grieving humans. While we found some effects of relationship type on DRD1 and DRD2 expression in some of these regions, loss of a high-quality opposite-sex relationship had a significant effect on DA receptor expression, with pair-bonded/loss males having higher expression in the aIC and ACC compared with pair-bonded/intact and nonbonded/loss males. Together, these data suggest that both relationship type and relationship quality affect reunion-seeking behavior and motivational neurocircuits following social loss of a bonded partner.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12861","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10274164","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}