The acoustic properties, syllable structure, and syllable sequences of ultrasonic vocalizations (USVs) during neonatal opioid withdrawal in FVB/N mouse substrains.

Concomitant with the opioid epidemic, there has been a rise in pregnant women diagnosed with opioid use disorder and cases of infants born with neonatal opioid withdrawal syndrome (NOWS). NOWS refers to signs and symptoms following cessation of prenatal opioid exposure that comprise neurological, gastrointestinal, and autonomic system dysfunction. A critical indicator of NOWS severity is excessive, high-pitched crying.

Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.

Sensitivity to the subjective reinforcing properties of opioids has a genetic component and can predict addiction liability of opioid compounds. We previously identified as a candidate gene underlying increased brain concentration of the oxycodone () metabolite oxymorphone () in BALB/cJ () versus BALB/cByJ () females that could increase OXY state-dependent reward. A large structural intronic variant is associated with a robust reduction of Zhx2 expression in J mice, which we hypothesized enhances OMOR levels and OXY addiction-like behaviors.

The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.

Rationale: Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Variability in NOWS severity necessitates a more individualized treatment approach.

and are candidate genes underlying sensitivity to oxycodone-induced locomotor activation and withdrawal-induced anxiety-like behaviors in C57BL/6 substrains.

Opioid use disorder is heritable, yet its genetic etiology is largely unknown. C57BL/6J and C57BL/6NJ mouse substrains exhibit phenotypic diversity in the context of limited genetic diversity which together can facilitate genetic discovery. Here, we found C57BL/6NJ mice were less sensitive to oxycodone (OXY)-induced locomotor activation versus C57BL/6J mice in a conditioned place preference paradigm.

Decreased myelin-related gene expression in the nucleus accumbens during spontaneous neonatal opioid withdrawal in the absence of long-term behavioral effects in adult outbred CFW mice.

Prenatal opioid exposure is a major health concern in the United States, with the incidence of neonatal opioid withdrawal syndrome (NOWS) escalating in recent years. NOWS occurs upon cessation of in utero opioid exposure and is characterized by increased irritability, disrupted sleep patterns, high-pitched crying, and dysregulated feeding. The main pharmacological strategy for alleviating symptoms is treatment with replacement opioids.

Decreased myelin-related gene expression in the nucleus accumbens during spontaneous neonatal opioid withdrawal in the absence of long-term behavioral effects in adult outbred CFW mice.

Unlabelled: Prenatal opioid exposure is a major health concern in the United States, with the incidence of neonatal opioid withdrawal syndrome (NOWS) escalating in recent years. NOWS occurs upon cessation of opioid exposure and is characterized by increased irritability, disrupted sleep patterns, high-pitched crying, and dysregulated feeding. The main pharmacological strategy for alleviating symptoms is treatment with replacement opioids.

Assessment of Binge-Like Eating of Unsweetened vs. Sweetened Chow Pellets in BALB/c Substrains.

Binge eating disorder (BED) is defined as chronic episodes of consuming large amounts of food in less than 2 h. Binge eating disorder poses a serious public health problem, as it increases the risk of obesity, type II diabetes, and heart disease. Binge eating is a highly heritable trait; however, its genetic basis remains largely unexplored.

Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward.

Understanding the pharmacogenomics of opioid metabolism and behavior is vital to therapeutic success, as mutations can dramatically alter therapeutic efficacy and addiction liability. We found robust, sex-dependent BALB/c substrain differences in oxycodone behaviors and whole brain concentration of oxycodone metabolites. BALB/cJ females showed robust state-dependent oxycodone reward learning as measured via conditioned place preference when compared with the closely related BALB/cByJ substrain.

Effect of Prenatal Opioid Exposure on the Human Placental Methylome.

Prenatal exposure to addictive drugs can lead to placental epigenetic modifications, but a methylome-wide evaluation of placental DNA methylation changes after prenatal opioid exposure has not yet been performed. Placental tissue samples were collected at delivery from 19 opioid-exposed and 20 unexposed control full-term pregnancies. Placental DNA methylomes were profiled using the Illumina Infinium HumanMethylationEPIC BeadChip.

Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross.

Thermal nociception involves the transmission of temperature-related noxious information from the periphery to the CNS and is a heritable trait that could predict transition to persistent pain. Rodent forward genetics complement human studies by controlling genetic complexity and environmental factors, analysis of end point tissue, and validation of variants on appropriate genetic backgrounds. Reduced complexity crosses between nearly identical inbred substrains with robust trait differences can greatly facilitate unbiased discovery of novel genes and variants.

Placental DNA methylation and associations with neonatal opioid withdrawal syndrome, a pilot study.

Aims: Epigenetic variation of DNA methylation of the mu-opioid receptor gene () has been identified in the blood and saliva of individuals with opioid use disorder (OUD) and infants with neonatal opioid withdrawal syndrome (NOWS). It is unknown whether epigenetic variation in exists within placental tissue in women with OUD and whether it is associated with NOWS outcomes. In this pilot study, the authors aimed to 1) examine the association between placental DNA methylation levels and NOWS outcomes, and 2) compare methylation levels in opioid-exposed non-exposed control placentas.

5' UTR variants in the quantitative trait gene Hnrnph1 support reduced 5' UTR usage and hnRNP H protein as a molecular mechanism underlying reduced methamphetamine sensitivity.

We previously identified a 210 kb region on chromosome 11 (50.37-50.58 Mb, mm10) containing two protein-coding genes (Hnrnph1, Rufy1) that was necessary for reduced methamphetamine-induced locomotor activity in C57BL/6J congenic mice harboring DBA/2J polymorphisms.

The effect of the demyelinating agent cuprizone on binge-like eating of sweetened palatable food in female and male C57BL/6 substrains.

Binge eating is a heritable symptom of eating disorders with an unknown genetic etiology. Rodent models for binge-like eating (BLE) of palatable food permit the study of genetic and biological mechanisms. We previously genetically mapped a coding mutation in Cyfip2 associated with increased BLE of sweetened palatable food in the C57BL/6NJ versus C57BL/6J substrain.

A Mutation in That Decreases Methamphetamine-Induced Reinforcement, Reward, and Dopamine Release and Increases Synaptosomal hnRNP H and Mitochondrial Proteins.

Individual variation in the addiction liability of amphetamines has a heritable genetic component. We previously identified (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying decreased methamphetamine-induced locomotor activity in mice. Here, we showed that mice (both females and males) with a heterozygous mutation in the first coding exon of (H1) showed reduced methamphetamine reinforcement and intake and dose-dependent changes in methamphetamine reward as measured via conditioned place preference.

Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Genetic Background, Parent-of Origin, and Sex.

Binge eating (BE) is a heritable trait associated with eating disorders and involves episodes of rapid, large amounts of food consumption. We previously identified cytoplasmic FMR1-interacting protein 2 () as a genetic factor underlying compulsive-like BE in mice. is a homolog of which is one of four paternally-deleted genes in patients with Type I Prader-Willi Syndrome (PWS), a neurodevelopmental disorder whereby 70% of cases involve paternal 15q11-q13 deletion.

Changes in neuronal immunofluorescence in the C- versus N-terminal domains of hnRNP H following D1 dopamine receptor activation.

RNA binding proteins are a diverse class of proteins that regulate all aspects of RNA metabolism. Accumulating studies indicate that heterogeneous nuclear ribonucleoproteins are associated with cellular adaptations in response to drugs of abuse. We recently mapped and validated heterogeneous nuclear ribonucleoprotein H1 (Hnrnph1) as a quantitative trait gene underlying differential behavioral sensitivity to methamphetamine.

Exercise-associated changes in the corticosterone response to acute restraint stress: evidence for increased adrenal sensitivity and reduced corticosterone response duration.

Exercise promotes stress resistance and is associated with reduced anxiety and reduced depression in both humans and in animal models. Despite the fact that dysfunction within the hypothalamic pituitary adrenal (HPA) axis is strongly linked to both anxiety and depressive disorders, the evidence is mixed as to how exercise alters the function of the HPA axis. Here we demonstrate that 4 weeks of voluntary wheel running was anxiolytic in C57BL/6J mice and resulted in a shorter time to peak corticosterone (CORT) and a more rapid decay of CORT following restraint stress.