Genes Brain and Behavior最新文献

{"title":"Stress enhances aggression in male rats with genetic stress hyper-reactivity","authors":"Aspen M. Harter,&nbsp;Chris Kim,&nbsp;Anna Yamazaki,&nbsp;Luca Lee,&nbsp;Michelle T. Ji,&nbsp;Mariya Nemesh,&nbsp;Eva E. Redei","doi":"10.1111/gbb.70005","DOIUrl":"https://doi.org/10.1111/gbb.70005","url":null,"abstract":"<p>The current study investigated stress-induced aggressive behavior in the resident-intruder test in males of the genetically stress hyper-reactive Wistar Kyoto More Immobile (WMI), and the nearly isogenic, control Wistar Kyoto Less Immobile (WLI) strains. Tests were carried out against same-age intruders during adolescence, and same-age and juvenile intruders in adulthood. In adolescence and adulthood, prior acute restraint stress decreased social interactions and decreased aggressive behaviors of adolescents and adult WLIs. However, prior stress precipitated aggression in the adult WMI males toward both same-age, and juvenile intruders compared with control WMIs and WLIs. Trunk blood levels of testosterone and androstenedione increased in stressed WLIs, but not in WMIs, suggesting no direct role of androgens in the increased aggression of WMIs. Expressions of aggression-relevant genes showed patterns commensurate with being causative in aggressive behavior. The methyl-CpG binding protein 2 was lower in the frontal cortex of control WMIs, and in the amygdala of stressed WMIs compared with their respective WLIs. Frontal cortex expression of vasopressin receptor 1a and serotonin transporter increased, solely in WMI males after stress. As behaviors were the same toward same-age and non-threatening juvenile intruders, the stress-induced increase in confrontational behavior of the adult WMI male was not because of enhanced fear or anxiety. These results suggest that genetic stress hyper-reactivity is a risk factor for stress-induced increases in aggression in males. Additionally, as known aggression-related genes showed expression patterns paralleling aggressive behavior, this model system could identify novel molecular pathways leading to stress-enhanced aggression.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451154","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 role of cerebellar FOXP1 in the development of motor and communicative behaviors in mice","authors":"R. Chasse,&nbsp;R. McLeod,&nbsp;A. Surian,&nbsp;R. H. Fitch,&nbsp;J. Li","doi":"10.1111/gbb.70001","DOIUrl":"https://doi.org/10.1111/gbb.70001","url":null,"abstract":"<p>The gene <i>FOXP2</i> is well established for a role in human speech and language; far less is known about <i>FOXP1</i>. However, this related gene has also been implicated in human language development as well as disorders associated with features of autism spectrum disorder (ASD). FOXP1 protein expression has also recently been identified in the cerebellum—a neural structure previously shown to express FOXP2 protein. The current study sought to elucidate the behavioral implications of a conditional knock-out of <i>Foxp1</i> using an <i>En1-Cre</i> driver, which is active in the entirety of the cerebellum and a subset of neurons in the midbrain and spinal cord, in mice using a test battery including motor tasks associated with cerebellar dysfunction, as well as communicative and autistic-relevant behaviors. Male and female mice with a conditional knock-out (cKO, <i>n</i> = 31) and wildtype littermate controls (WT, <i>n</i> = 34) were assessed for gross and orofacial motor control, motor-coordination learning, locomotion, social behavior, anxiety, auditory processing and expressive vocalizations. Overall results suggest <i>Foxp1</i> plays a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex. Robust motor deficits associated with Foxp1 protein loss may particularly affect vocalizations based on significant orofacial motor deficits in cKO subjects could also contribute to vocalization anomalies. In summary, the current study provides key insights into the role of <i>Foxp1</i> in cerebellar function and associated behaviors in mice, with implications for an improved understanding of communicative and motor-based neurodevelopmental disabilities in humans.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443372","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":"Concentration- and time-dependent behavioural effects of ethanol on Lumbriculus variegatus","authors":"Aidan Seeley,&nbsp;Romessa Mahmood,&nbsp;Caitlin Bellamy,&nbsp;Elis G. Roome,&nbsp;Benjamin S. Williams,&nbsp;Nia A. Davies,&nbsp;Melisa J. Wallace","doi":"10.1111/gbb.70006","DOIUrl":"https://doi.org/10.1111/gbb.70006","url":null,"abstract":"<p>Ethanol is one of the most widely used drugs in the world. Ethanol induces profound physiological and behavioural responses in invertebrate model organisms, such as <i>Caenorhabditis elegans</i> and <i>Drosophila melanogaster</i>. <i>Lumbriculus variegatus</i> (Annelida, Oligochaete) is an aquatic worm which shows behavioural responses to common drugs and thus is potentially useful in pharmacological research. The effects of ethanol are unknown in this organism. In this study, we examine the effects of acute exposure to ethanol (0–500 mM) on the stereotypical movements and locomotor activity of <i>L. variegatus</i> and examine the concentration- (0–500 mM) and time-dependent (0–210 min) effects of ethanol in <i>L. variegatus</i>. We show that ≥250 mM ethanol reversibly reduced the ability of tactile stimulation to elicit stereotypical movements, namely body reversal and helical swimming and locomotor activity (<i>p</i> &lt; 0.05, <i>N</i> = 8). We also found that 2 min of exposure to ≥250 mM ethanol rapidly induces steady-state hypokinesis (<i>p</i> &lt; 0.05, <i>N</i> = 11) and confirm ethanol absorption into <i>L. variegatus</i> tissues. Additionally, we also observed acute ethanol tolerance after 150 min of exposure to 500 mM ethanol (<i>p</i> &lt; 0.05, <i>N</i> = 24). This study is the first to report the behavioural effects of ethanol in <i>L. variegatus</i>. Our results show that this is a model organism for use in ethanol studies, providing further evidence for its utility in pharmacological research.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443373","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 GWAS for grip strength in cohorts of children—Advantages of analysing young participants for this trait","authors":"Filippo Abbondanza,&nbsp;Carol A. Wang,&nbsp;Judith Schmitz,&nbsp;Krzysztof Marianski,&nbsp;Craig E. Pennell,&nbsp;Andrew J. O. Whitehouse,&nbsp;Silvia Paracchini","doi":"10.1111/gbb.70003","DOIUrl":"10.1111/gbb.70003","url":null,"abstract":"<p>Grip strength (GS) is a proxy measure for muscular strength and a predictor for bone fracture risk among other diseases. Previous genome-wide association studies (GWASs) have been conducted in large cohorts of adults focusing on scores collected for the dominant hand, therefore increasing the likelihood of confounding effects by environmental factors. Here, we perform the first GWAS meta-analyses on maximal GS with the dominant (GSD) and non-dominant (GSND) hand in two cohorts of children (ALSPAC, <i>N</i> = 5450; age range = 10.65–13.61; Raine Study, <i>N</i> = 1162, age range: 9.42–12.38 years). We identified a novel significant association for GSND (rs9546244, <i>LINC02465</i>, <i>p</i> = 3.43e−08<i>)</i> and replicated associations previously reported in adults including with a <i>HOXB3</i> gene marker that shows an expression quantitative trait locus (eQTL) effect. Despite a much smaller sample (~3%) compared with the UK Biobank we replicated correlation analyses previously reported in this much larger adult cohort, such as a negative correlation with coronary artery disease. Although the results from the polygenic risk score (PRS) analyses did not survive multiple testing correction, we observed nominally significant associations between GS and risk of overall fracture, as previously reported, as well ADHD which will require further investigations. Finally, we observed a higher SNP-heritability (24%–41%) compared with previous studies (4%–24%) in adults. Overall, our results suggest that cohorts of children might be better suited for genetic studies of grip strength, possibly due to the shorter exposure to confounding environmental factors compared with adults.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394899","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":"Mical1 deletion in tyrosinase expressing cells affects mouse running gaits","authors":"Katarina Micovic,&nbsp;Alicia Canuel,&nbsp;Aasiya Remtulla,&nbsp;Alexandre Chuyen,&nbsp;Margarita Byrsan,&nbsp;David J. McGarry,&nbsp;Michael F. Olson","doi":"10.1111/gbb.70004","DOIUrl":"10.1111/gbb.70004","url":null,"abstract":"<p>Neuronal development is a highly regulated process that is dependent on the correct coordination of cellular responses to extracellular cues. In response to semaphorin axon guidance proteins, the MICAL1 protein is stimulated to produce reactive oxygen species that oxidize actin on specific methionine residues, leading to filamentous actin depolymerization and consequent changes in neuronal growth cone dynamics. Crossing genetically modified mice homozygous for floxed <i>Mical1</i> (<i>Mical1</i>^<i>fl/fl</i>) alleles with transgenic mice expressing Cre recombinase under the control of a <i>tyrosinase</i> gene enhancer/promoter (<i>Tyr::Cre</i>) enabled conditional <i>Mical1</i> deletion. Immunohistochemical analysis showed <i>Mical1</i> expression in the cerebellum, which plays a prominent role in the coordination of motor movements, with reduced <i>Mical1</i> expression in <i>Mical1</i>^<i>fl/fl</i> mice co-expressing <i>Tyr::Cre</i>. Analysis of the gaits of mice running on a treadmill showed that both male and female <i>Mical1</i>^<i>fl/fl</i>, <i>Tyr::Cre</i> mutant mice had significant alterations to their striding patterns relative to wild-type mice, although the specific aspects of their altered gaits differed between the sexes. Additional motor tests that involved movement on a rotating rod, descending a vertical pole, or crossing a balance beam did not show significant differences between the genotypes, suggesting that the effect of the <i>Mical1</i>^<i>fl/fl</i>, <i>Tyr::Cre</i> genetic modifications was only manifested during specific highly coordinated movements that contribute to running. These findings indicate that there is a behavioral consequence in <i>Mical1</i>^<i>fl/fl</i>, <i>Tyr::Cre</i> mutant mice that affects motor control as manifested by alterations in their gait.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331600","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":"Cognitive behavioral phenotyping of DSCAM heterozygosity as a model for autism spectrum disorder","authors":"Ryan C. Neff,&nbsp;Katherine A. Stangis,&nbsp;Ujjawal Beniwal,&nbsp;Ty Hergenreder,&nbsp;Bing Ye,&nbsp;Geoffrey G. Murphy","doi":"10.1111/gbb.70002","DOIUrl":"10.1111/gbb.70002","url":null,"abstract":"<p>It is estimated that 1 in 36 children are affected by autism spectrum disorder (ASD) in the United States, which is nearly a twofold increase from a decade ago. Recent genetic studies have identified de novo loss-of-function (dnLoF) mutations in the <i>Down Syndrome Cell Adhesion Molecule (DSCAM)</i> as a strong risk factor for ASD. Previous research has shown that <i>DSCAM</i> ablation confers social interaction deficits and perseverative behaviors in mouse models. However, it remains unknown to what extent <i>DSCAM</i> underexpression captures the full range of behaviors, specifically cognitive phenotypes, presented in ASD. Here, we conducted a comprehensive cognitive behavioral phenotyping which revealed that loss of one copy of <i>DSCAM</i>, as in the <i>DSCAM</i>^2J+/−, that is, <i>DSCAM</i> heterozygous mice, displayed hyperactivity, increased anxiety-like behavior, and motor coordination deficits. Additionally, hippocampal-dependent learning and memory was affected, including impairments in working memory, long-term memory, and contextual fear learning. Interestingly, implicit learning processes remained intact. Therefore, <i>DSCAM</i> LoF produces autistic-like behaviors that are similar to those observed in human cases of ASD. These findings further support a role for <i>DSCAM</i> dnLoF mutations in ASD and suggest <i>DSCAM</i>^2J+/− as a suitable model for ASD research.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249027","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":"Divergent neural nodes are species- and hormone-dependent in the brood parasitic brain","authors":"Fernanda G. Duque,&nbsp;Asma Azam,&nbsp;Amanpreet Kaur,&nbsp;Rachel Pao,&nbsp;Kathleen S. Lynch","doi":"10.1111/gbb.12907","DOIUrl":"10.1111/gbb.12907","url":null,"abstract":"<p>Avian brood parasitism is an evolutionarily derived behavior for which the neurobiological mechanisms are mostly unexplored. We aimed to identify brain regions that have diverged in the brood-parasitic brain using relative transcript abundance of social neuropeptides and receptors. We compared behavioral responses and transcript abundance in three brain regions in the brown-headed cowbird (BHCO), a brood parasite, and a closely related parental species, the red-winged blackbird (RWBL). Females of both species were treated with mesotocin (MT; avian homolog of oxytocin) or saline prior to exposure to nest stimuli. Results reveal that MT promotes approach toward nests with eggs rather than nests with begging nestlings in both species. We also examined relative transcript abundance of the five social neuropeptides and receptors in the brain regions examined: preoptic area (POA), paraventricular nucleus (PVN) and bed nucleus of the stria terminalis (BST). We found that MT-treated cowbirds but not blackbirds exhibited lower transcript abundance for two receptors, corticotropin-releasing factor 2 (CRFR2) and prolactin receptor (PRLR) in BST. Additionally, MT-treated cowbirds had higher PRLR in POA, comparable to those found in blackbirds, regardless of treatment. No other transcripts of interest exhibited significant differences as a result of MT treatment, but we found a significant effect of species in the three regions. Together, these results indicate that POA, PVN, and BST represent neural nodes that have diverged in avian brood parasites and may serve as neural substrates of brood-parasitic behavior.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156548","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":"Commensal bacteria exacerbate seizure-like phenotypes in Drosophila voltage-gated sodium channel mutants","authors":"Patrick Lansdon,&nbsp;Junko Kasuya,&nbsp;Toshihiro Kitamoto","doi":"10.1111/gbb.70000","DOIUrl":"10.1111/gbb.70000","url":null,"abstract":"<p>Mutations in voltage-gated sodium (Na_v) channels, which are essential for generating and propagating action potentials, can lead to serious neurological disorders, such as epilepsy. However, disease-causing Na_v channel mutations do not always result in severe symptoms, suggesting that the disease conditions are significantly affected by other genetic factors and various environmental exposures, collectively known as the “exposome”. Notably, recent research emphasizes the pivotal role of commensal bacteria in neural development and function. Although these bacteria typically benefit the nervous system under normal conditions, their impact during pathological states remains largely unknown. Here, we investigated the influence of commensal microbes on seizure-like phenotypes exhibited by <i>para</i>^<i>Shu</i>—a gain-of-function mutant of the <i>Drosophila</i> Na_v channel gene, <i>paralytic</i>. Remarkably, the elimination of endogenous bacteria considerably ameliorated neurological impairments in <i>para</i>^<i>Shu</i>. Consistently, reintroducing bacteria, specifically from the <i>Lactobacillus</i> or <i>Acetobacter</i> genera, heightened the phenotypic severity in the bacteria-deprived mutants. These findings posit that particular native bacteria contribute to the severity of seizure-like phenotypes in <i>para</i>^<i>Shu</i>. We further uncovered that treating <i>para</i>^<i>Shu</i> with antibiotics boosted Nrf2 signaling in the gut, and that global Nrf2 activation mirrored the effects of removing bacteria from <i>para</i>^<i>Shu</i>. This raises the possibility that the removal of commensal bacteria suppresses the seizure-like manifestations through augmented antioxidant responses. Since bacterial removal during development was critical for suppression of adult <i>para</i>^<i>Shu</i> phenotypes, our research sets the stage for subsequent studies, aiming to elucidate the interplay between commensal bacteria and the developing nervous system in conditions predisposed to the hyperexcitable nervous system.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134345","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":"Transcriptomics analysis reveals potential regulatory role of nSMase2 (Smpd3) in nervous system development and function of middle-aged mouse brains","authors":"Zhihui Zhu,&nbsp;Timothy S. McClintock,&nbsp;Erhard Bieberich","doi":"10.1111/gbb.12911","DOIUrl":"10.1111/gbb.12911","url":null,"abstract":"<p>Neutral sphingomyelinase-2 (nSMase2), gene name sphingomyelin phosphodiesterase-3 (<i>Smpd3</i>), is a key regulatory enzyme responsible for generating the sphingolipid ceramide. The function of nSMase2 in the brain is still controversial. To better understand the functional roles of nSMase2 in the aging mouse brain, we applied RNA-seq analysis, which identified a total of 1462 differentially abundant mRNAs between <i>+/fro and fro/fro</i>, of which 891 were increased and 571 were decreased in nSMase2-deficient mouse brains. The most strongly enriched GO and KEGG annotation terms among transcripts increased in <i>fro/fro</i> mice included synaptogenesis, synapse development, synaptic signaling, axon development, and axonogenesis. Among decreased transcripts, enriched annotations included ribosome assembly and mitochondrial protein complex functions. KEGG analysis of decreased transcripts also revealed overrepresentation of annotations for Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington disease (HD). Ingenuity Pathway Analysis (IPA) tools predicted lower susceptibility to these neurodegenerative disorders, as well as predictions agreeing with stronger synaptic function, learning, and memory in <i>fro/fro</i> mice. The IPA tools identified signaling proteins, epigenetic regulators, and microRNAs as likely upstream regulators of the broader set of genes encoding the affected transcripts. It also revealed 16 gene networks, each linked to biological processes identified as overrepresented annotations among the affected transcripts by multiple analysis methods. Therefore, the analysis of these RNA-seq data indicates that nSMase2 impacts synaptic function and neural development, and may contribute to the onset and development of neurodegenerative diseases in middle-aged mice.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019453","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 activity-regulated cytoskeleton-associated protein (Arc) functions in a cell type- and sex-specific manner in the adult nucleus accumbens to regulate non-contingent cocaine behaviors","authors":"Daniel J. Wood,&nbsp;Jessica L. Huebschman,&nbsp;Dalia Martinez,&nbsp;Evgeny Tsvetkov,&nbsp;Kirsten Snyder,&nbsp;Raymond Tjhia,&nbsp;Jaswinder Kumar,&nbsp;Brandon W. Hughes,&nbsp;Makoto Taniguchi,&nbsp;Laura N. Smith,&nbsp;Christopher W. Cowan,&nbsp;Rachel D. Penrod","doi":"10.1111/gbb.12910","DOIUrl":"10.1111/gbb.12910","url":null,"abstract":"<p>Repeated cocaine use produces adaptations in brain function that contribute to long-lasting behaviors associated with cocaine use disorder (CUD). In rodents, the activity-regulated cytoskeleton-associated protein (Arc) can regulate glutamatergic synaptic transmission, and cocaine regulates Arc expression and subcellular localization in multiple brain regions, including the nucleus accumbens (NAc)—a brain region linked to CUD-related behavior. We show here that repeated, non-contingent cocaine administration in global <i>Arc</i> KO male mice produced a dramatic hypersensitization of cocaine locomotor responses and drug experience-dependent sensitization of conditioned place preference (CPP). In contrast to the global <i>Arc</i> KO mice, viral-mediated reduction of Arc in the adult male, but not female, NAc (shArc^NAc) reduced both CPP and cocaine-induced locomotor activity, but without altering basal miniature or evoked glutamatergic synaptic transmission. Interestingly, cell type-specific knockdown of Arc in D1 dopamine receptor-expressing NAc neurons reduced cocaine-induced locomotor sensitization, but not cocaine CPP; whereas, Arc knockdown in D2 dopamine receptor-expressing NAc neurons reduced cocaine CPP, but not cocaine-induced locomotion. Taken together, our findings reveal that global, developmental loss of Arc produces hypersensitized cocaine responses; however, these effects cannot be explained by Arc's function in the adult mouse NAc since Arc is required in a cell type- and sex-specific manner to support cocaine-context associations and locomotor responses.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009831","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}