A5063608221- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Estrogen and related hormone effects
- Neuroinflammation and Neurodegeneration Mechanisms
- Proteoglycans and glycosaminoglycans research
- Peroxisome Proliferator-Activated Receptors
- Zebrafish Biomedical Research Applications
- Alcohol Consumption and Health Effects
- Adipose Tissue and Metabolism
- Tryptophan and brain disorders
- Ion channel regulation and function
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Neuroendocrine regulation and behavior
- Hypothalamic control of reproductive hormones
- Neuropeptides and Animal Physiology
- Memory and Neural Mechanisms
- Neurobiology and Insect Physiology Research
- Histone Deacetylase Inhibitors Research
- Invertebrate Immune Response Mechanisms
- Menopause: Health Impacts and Treatments
- Protein Tyrosine Phosphatases
- Neurogenesis and neuroplasticity mechanisms
University of Illinois Chicago
2015-2024
Virginia Commonwealth University
2023-2024
University of California, San Francisco
2007-2017
Queensland University of Technology
2017
Johns Hopkins University
2017
National Institute on Alcohol Abuse and Alcoholism
2017
National Institutes of Health
2017
National Institute on Drug Abuse
2017
University of Chicago
2017
Brown University
2017
Background Recently, the incidence of binge drinking by women has increased. Binge is detrimental to women's health, yet biological mechanisms that promote excessive are not well understood. One method assessing binge‐like ethanol (Et OH ) consumption in mice dark ( DID test, which drink sufficient Et achieve intoxication. In this study, we directly compared male, female, and ovariectomized OVX for tested whether 17 β ‐estradiol (E2) contributes . We also measured varies throughout estrous...
Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. exposure induces epigenetic reprogramming at the enhancer region of activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as synaptic activity response element (SARE), and decreases Arc expression amygdala both rodents humans. The causal role amygdalar epigenomic regulation SARE adult anxiety after adolescent unknown. Here, we show that...
Estrogens promote binge alcohol drinking and contribute to sex differences in use disorder. However, the mechanisms are largely unknown. This study aims test if estrogens act on 5-hydroxytryptamine neurons dorsal raphe nucleus (5-HT
It remains unclear to what extent drugs targeting transcriptional repressor complexes affect global gene expression in cells derived from target and nontarget human tissues. To address this question, we used genome-wide analysis using microarrays analyze the response of three tumor one normal epithelial cell line treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR). Notably, found that 5-aza-CdR induced a limited number genes (mean, 0.67%; range, 0.17-1.8% 25,940...
Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes receptor tyrosine commonly known for its oncogenic function various human cancers. We have determined Alk associated with altered behavioral responses to ethanol fruit fly Drosophila melanogaster, mice, and humans. Mutant flies containing transposon insertions dAlk demonstrate increased resistance sedating effect of ethanol. Database analyses revealed expression levels brains recombinant inbred mice are...
Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2), predominant form of circulating estrogen pre-menopausal females, increases ethanol consumption, suggesting that E2 affect rewarding properties and thus development alcohol use disorder females. The ventral tegmental area (VTA) is critically involved reinforcing effects ethanol. In order to determine role VTA physiology, gonadally intact female mice...
Toll-like receptor 4 (TLR4) is a critical component of innate immune signaling and has been implicated in alcohol responses preclinical clinical models. Members the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium tested hypothesis that TLR4 mediates excessive ethanol drinking using following models: (1) Tlr4 knock-out (KO) rats, (2) selective knockdown mRNA mouse nucleus accumbens (NAc), (3) injection antagonist (+)-naloxone mice. Lipopolysaccharide (LPS)...
Background Alcohol exposure leads to changes in the extracellular matrix (ECM) brain, which profoundly impacts neuronal plasticity. Perineuronal nets (PNs) are specialized ECM structures that enclose subpopulations of neurons cortex. Adolescent alcohol induces long-lasting increases expression PN components cortex adult mice. However, it has not been determined whether binge young adults alters PNs. Here, we examined PNs and their core insula primary motor after repeated binge-like ethanol...
Abstract One of the most pernicious characteristics alcohol use disorder is compulsion to drink despite negative consequences. The insular cortex controls decision making under conditions risk or conflict. Cortical activity tightly controlled by inhibitory interneurons that are often enclosed specialized extracellular matrix structures known as perineuronal nets (PNNs), which regulate neuronal excitability and plasticity. density PNNs in insula increases after repeated bouts binge drinking,...
Elevations in estrogen (17β-estradiol, E2) are associated with increased alcohol drinking by women and experimentally rodents. E2 alters the activity of dopamine system, including VTA its projection targets, which plays an important role binge drinking. A previous study demonstrated that, during high states, neurons female mice more sensitive to ethanol excitation. However, mechanisms responsible for ability enhance sensitivity have not been investigated. In this study, we used selective...
Compulsive alcohol drinking is a key symptom of use disorder (AUD) that particularly resistant to treatment. An understanding the biological factors underly compulsive will allow for development new therapeutic targets AUD. One animal model involves addition bitter-tasting quinine an ethanol solution and measuring willingness consume despite aversive taste. Previous studies have demonstrated this type aversion-resistant modulated in insular cortex male mice by specialized condensed...
Pharmacological and genetic studies have implicated the mu opioid receptor (MOR) in regulation of ethanol intake animal models humans. Non-specific antagonists receptors been shown to affect consumption when infused directly into ventral tegmental area (VTA) rats. However, administration MOR-selective VTA has yielded mixed results. We used RNA interference (RNAi) specifically decrease levels MOR messenger mice examined effect on a two-bottle choice paradigm. Mice were injected with...
Men and women respond differently to the subjective effects of cocaine cocaine-associated cues, which has implications for development maintenance addiction. Preclinical studies performed in rats, modeling various aspects addiction, have largely validated these results, indicating that female rats may be more sensitive rewarding properties cocaine. The molecular mechanisms leading sex differences reward not been determined, although hormones are thought play a role. mouse is commonly used as...
The clinical steroidal selective estrogen receptor (ER) degrader (SERD), fulvestrant, is effective in metastatic breast cancer, but limited by poor pharmacokinetics, prompting the development of orally bioavailable, nonsteroidal SERDs, currently trials. These trials address local cancer as well peripheral metastases, patients with brain metastases are generally excluded because lack blood–brain barrier penetration. A novel family benzothiophene SERDs a basic amino side arm (B-SERDs) was...
Previously, we showed that the mouse LIM-domain only 4 ( Lmo4 ) gene, which encodes a protein containing two zinc-finger LIM domains interact with various DNA-binding transcription factors, attenuates behavioral sensitivity to repeated cocaine administration. Here show of anaplastic lymphoma kinase Alk is repressed by LMO4 in striatum and promotes development sensitization conditioned place preference, measure reward. Since known estrogen receptor α (ERα) at promoters target genes,...
Previous work from our laboratory demonstrated a role for the Drosophila Lim-only (dLmo) gene in regulating behavioral responses to cocaine. Herein, we examined whether dLmo influences flies' sensitivity ethanol's sedating effects. We also investigated 1 of mammalian homologs dLmo, Lmo3, is involved ethanol mice.To examine function ethanol-induced sedation, mutant flies with reduced or increased expression were tested using loss righting (LOR) assay. To determine mouse Lmo3 regulates...
Abstract Anaplastic lymphoma kinase (ALK) is a receptor tyrosine associated with alcohol dependence in humans and behavioral responses to ethanol mice. To characterize the ability of ALK control consumption, we treated mice inhibitors TAE684 or alectinib before testing them for binge‐like drinking using dark protocol. Mice drank less than controls. In addition, treatment abolished conditioned place preference, indicating that regulates rewarding properties ethanol. Because ventral tegmental...