Digital Commons Network^™

Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka

Department of Neuroscience Faculty Papers

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the …

Sutherland, David (Fa 1056), Manuscripts & Folklife Archives

Folklife Archives Finding Aids

Finding aid only for Folklife Archives Project 1056. Student folk studies project titled: “Ghost Stories Western Students Tell,” which includes survey sheets with ghost tales in Fayette County, Indiana and in Allen County, Jefferson County, Warren County and Webster County, Kentucky. Sheets may include a ghost story, informant’s name and address, and motif index number.

The Reliability And Effectiveness Of A Radar-Based Animal Detection System, Marcel P. Huijser, Elizabeth R. Fairbank, Fernanda D. Abra

CESTiCC Project Reports

This document contains data on the reliability and effectiveness of an animal detection system along U.S. Hwy 95 near Bonners Ferry, Idaho. The system uses a Doppler radar to detect large mammals (e.g., deer and elk) when they approach the highway. The system met most of the suggested minimum norms for reliability. The total time the warning signs were activated was at most 90 seconds per hour, and likely substantially less. Animal detection systems are designed to detect an approaching animal. After an animal has been detected, warning signs are activated which allow drivers to respond. Results showed that 58.1–67.9% …

Insights Into Onchocerca Volvulus Population Biology Through Multilocus Immunophenotyping, Carmelle T Norice-Tra, José Ribeiro, Sasisekhar Bennuru, Michael P Fay, Rahul Tyagi, Makedonka Mitreva, Thomas B Nutman

2010-2019 OA Pubs

We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides …

Mutations Of Conserved Non-Coding Elements Of Pitx2 In Patients With Ocular Dysgenesis And Developmental Glaucoma., Meredith E. Protas, Eric Weh, Tim Footz, Jay Kasberger, Scott C. Baraban, Alex V. Levin, L. Jay Katz, Robert Ritch, Michael A. Walter, Elena V. Semina, Douglas B. Gould

Natural Sciences and Mathematics | Faculty Scholarship

Mutations in FOXC1 and PITX2 constitute the most common causes of ocular anterior segment dysgenesis (ASD), and confer a high risk for secondary glaucoma. The genetic causes underlying ASD in approximately half of patients remain unknown, despite many of them being screened by whole exome sequencing. Here, we performed whole genome sequencing on DNA from two affected individuals from a family with dominantly inherited ASD and glaucoma to identify a 748-kb deletion in a gene desert that contains conserved putative PITX2 regulatory elements. We used CRISPR/Cas9 to delete the orthologous region in zebrafish in order to test the pathogenicity of …

Design, Synthesis, And Biological Activity Of 5'-Phenyl-1,2,5,6-Tetrahydro-3,3'-Bipyridine Analogues As Potential Antagonists Of Nicotinic Acetylcholine Receptors, Yafei Jin, Xiaoqin Huang, Roger L. Papke, Emily M. Jutkiewicz, Hollis D Showalter, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

Starting from a known non-specific agonist (1) of nicotinic acetylcholine receptors (nAChRs), rationally guided structural-based design resulted in the discovery of a small series of 5′-phenyl-1,2,5,6-tetrahydro-3,3′-bipyridines (3a – 3e) incorporating a phenyl ring off the pyridine core of 1. The compounds were synthesized via successive Suzuki couplings on a suitably functionalized pyridine starting monomer 4 to append phenyl and pyridyl substituents off the 3- and 5-positions, respectively, and then make subsequent modifications on the flanking pyridyl ring to provide target compounds. Compound 3a is a novel antagonist which is highly selective for α3β4 nAChR (K_i = 123 nM) …

Loss Of Fructose-1,6-Bisphosphatase Induces Glycolysis And Promotes Apoptosis Resistance Of Cancer Stem-Like Cells: An Important Role In Hexavalent Chromium-Induced Carcinogenesis, Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang

Toxicology and Cancer Biology Faculty Publications

Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance. BEAS-2B-Cr-CSC are metabolic inactive as evidenced by reductions in oxygen consumption, glucose uptake, ATP production, and lactate …

The 9th Conference On Metal Toxicity And Carcinogenesis: The Conference Overview, James T. F. Wise, Lei Wang, Zhuo Zhang, Xianglin Shi

Pharmacology and Nutritional Sciences Faculty Publications

Heavy metals, such as arsenic, chromium, cadmium, nickel, mercury, and uranium are known to cause many human diseases and health complications after occupational or environmental exposure. Consequently, metals are environmental health concerns. This manuscript is an overview of the 9th Conference on Metal Toxicity and Carcinogenesis held in October 2016 in Lexington, Kentucky. Since 2000, this biennial meeting brings together experts in the field to discuss current and prospective research in an effort to advance research pertaining to metal toxicity and carcinogenesis. In this review we summarize the major topics discussed and provide insight regarding current research in the field …

Gucy2c Signaling Opposes The Acute Radiation-Induced Gi Syndrome., Peng Li, Evan Wuthrick, Jeff A. Rappaport, Crystal Kraft, Jieru E. Lin, Glen Marszalowicz, Adam E. Snook, Tingting Zhan, Terry M. Hyslop, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

High doses of ionizing radiation induce acute damage to epithelial cells of the gastrointestinal (GI) tract, mediating toxicities restricting the therapeutic efficacy of radiation in cancer and morbidity and mortality in nuclear disasters. No approved prophylaxis or therapy exists for these toxicities, in part reflecting an incomplete understanding of mechanisms contributing to the acute radiation-induced GI syndrome (RIGS). Guanylate cyclase C (GUCY2C) and its hormones guanylin and uroguanylin have recently emerged as one paracrine axis defending intestinal mucosal integrity against mutational, chemical, and inflammatory injury. Here, we reveal a role for the GUCY2C paracrine axis in compensatory mechanisms opposing RIGS. …

Posttranscriptional Regulation Of Parg Mrna By Hur Facilitates Dna Repair And Resistance To Parp Inhibitors, Saswati N. Chand, Mahsa Zarei, M. J. Schiewer, Akshay R. Sanan, Carmella Romeo, Shruti Lal, Joseph A. Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric R. Londin, Wei Jiang, Nicole Meisner-Kober, Michael J. Pishvaian, Karen E. Knudsen, Charles Yeo, John M Pascal, Jordan M. Winter, Jonathan R. Brody

Department of Surgery Faculty Papers

The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9–mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3⁰ untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to …

Pituitary Genomic Expression Profiles Of Steers Are Altered By Grazing Of High Vs. Low Endophyte-Infected Tall Fescue Forages, Qing Li, Raquel Hegge, Phillip J. Bridges, James C. Matthews

Animal and Food Sciences Faculty Publications

Consumption of ergot alkaloid-containing tall fescue grass impairs several metabolic, vascular, growth, and reproductive processes in cattle, collectively producing a clinical condition known as “fescue toxicosis.” Despite the apparent association between pituitary function and these physiological parameters, including depressed serum prolactin; no reports describe the effect of fescue toxicosis on pituitary genomic expression profiles. To identify candidate regulatory mechanisms, we compared the global and selected targeted mRNA expression patterns of pituitaries collected from beef steers that had been randomly assigned to undergo summer-long grazing (89 to 105 d) of a high-toxic endophyte-infected tall fescue pasture (HE; 0.746 μg/g ergot alkaloids; …

Mitochondrial Phylogenomics Of Hemiptera Reveals Adaptive Innovations Driving The Diversification Of True Bugs, Hu Li, John Moeller Leavengood Jr., Eric G. Chapman, Daniel Burkhardt, Fan Song, Pei Jiang, Jinpeng Liu, Xuguo Zhou, Wanzhi Cai

Entomology Faculty Publications

Hemiptera, the largest non-holometabolous order of insects, represents approximately 7% of metazoan diversity. With extraordinary life histories and highly specialized morphological adaptations, hemipterans have exploited diverse habitats and food sources through approximately 300 Myr of evolution. To elucidate the phylogeny and evolutionary history of Hemiptera, we carried out the most comprehensive mitogenomics analysis on the richest taxon sampling to date covering all the suborders and infraorders, including 34 newly sequenced and 94 published mitogenomes. With optimized branch length and sequence heterogeneity, Bayesian analyses using a site-heterogeneous mixture model resolved the higher-level hemipteran phylogeny as (Sternorrhyncha, (Auchenorrhyncha, (Coleorrhyncha, Heteroptera))). Ancestral character …

A Global Staphylococcus Aureus Proteome Resource Applied To The In Vivo Characterization Of Host-Pathogen Interactions., Stephan Michalik, Maren Depke, Annette Murr, Manuela Gesell Salazar, Ulrike Kusebauch, Zhi Sun, Tanja C Meyer, Kristin Surmann, Henrike Pförtner, Petra Hildebrandt, Stefan Weiss, Laura Marcela Palma Medina, Melanie Gutjahr, Elke Hammer, Dörte Becher, Thomas Pribyl, Sven Hammerschmidt, Eric W Deutsch, Samuel L Bader, Michael Hecker, Robert L Moritz, Ulrike Mäder, Uwe Völker, Frank Schmidt

Articles, Abstracts, and Reports

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation …

Silver Oxide Coatings With High Silver-Ion Elution Rates And Characterization Of Bactericidal Activity., Sarah S Goderecci, Eric Kaiser, Michael Yanakas, Zachary Norris, Jeffrey Scaturro, Robert Oszust, Clarence D Medina, Fallon Waechter, Min Heon, Robert R Krchnavek, Lei Yu, Samuel E Lofland, Renee M Demarest, Gregory A Caputo, Jeffrey D Hettinger

Rowan-Virtua School of Osteopathic Medicine Departmental Research

This paper reports the synthesis and characterization of silver oxide films for use as bactericidal coatings. Synthesis parameters, dissolution/elution rate, and bactericidal efficacy are reported. Synthesis conditions were developed to create AgO, Ag₂O, or mixtures of AgO and Ag₂O on surfaces by reactive magnetron sputtering. The coatings demonstrate strong adhesion to many substrate materials and impede the growth of all bacterial strains tested. The coatings are effective in killing Escherichia coli and Staphylococcus aureus, demonstrating a clear zone-of-inhibition against bacteria growing on solid media and the ability to rapidly inhibit bacterial growth in planktonic culture. Additionally, the coatings exhibit very …

The Emperor's Ostrich, Rachel Waddam

Children's Book and Media Review

The young Emperor is going to take the throne, but Grandfather Spirit thinks he’s not ready, so he sends him off on an adventure accompanied by an ostrich to protect him. Grandmother Spirit has had enough of this meddling, so she sends Maid Begonia chasing after her errant cow. Along the way, Key, a boy who is bound to save damsels in distress, joins the group as the emperor’s ostrich and Begonia’s cow refuse to be separated. Back home, a trio of men are plotting to take the throne while Begonia’s mother sets out to find her daughter. All the …

Patterns In The Jungle, Cynthia Phillips

Children's Book and Media Review

There are patterns everywhere. All we need to do is look for them. This book introduces young children to patterns by pointing them out in the jungle. The scales on an iguana and the feathers on a peacock have patterns. Snakes, millipedes, tigers and even vines are great examples of patterns. What patterns do you see around you?

The Zoo Box, Cynthia Phillips

Children's Book and Media Review

Have you ever wondered what it would be like to reverse roles with zoo animals? This animated comic strip explores that possibility. Meet Erika and Patrick. Their parents are going out for the night and Erika is in charge. Mom has asked them to be in bed on time with the promise of going to the zoo in the morning. Erika and Patrick enjoy playing until they find a box that says “DO NOT OPEN.” Of course it must be a fun surprise. . .or is it? Once the box is opened zoo animals start coming out of it! The …

Search And Spot Animals!, Sydnee Burr

Children's Book and Media Review

In this early learning picture book for young children, puzzles meet the reader on every page. The colors and illustrations attract little eyes and fingers, making each page an exciting entrapment. From kittens to hens and puppies to horses, Search and Spot Animals utilizes a variety of shapes, colors, silhouettes, and tasks to keep young readers both entertained and curious.

Elmer And The Flood, Aylea Stephens

Children's Book and Media Review

It has been raining for days and Elmer, the patchwork elephant, is tired of being stuck inside a cave with the rest of his herd. Many animals suggest to him that he should come inside their caves because of the rain, but Elmer still wants to go for a walk. The jungle is partly flooded, but the crocodiles are excited to swim in new places and the ducks are enjoying the weather. Elmer learns that Young Elephant is missing, so he goes to rescue Young, who is stuck on an island. Elmer gets all of the other elephants to help …

I'Ll Wait, Mr. Panda, Ariel Woodbury

Children's Book and Media Review

Mr. Panda is making a surprise. His friends are very curious about what the surprise is, but waiting is boring and hard. Only Penguin stays to find out. His patience is rewarded with a GIANT doughnut!

Wilderness: An Interactive Atlas Of Animals, Ariel Woodbury

Children's Book and Media Review

Explore the amazing world of animals with this interactive book. Discover the panther chameleon in the rain forest, the sociable weaver bird of the savanna, and many other animals of the six main habitats. Each habitat introduces a bunch of animals and some little known facts about them.

The Elephant's Friend And Other Tales From Ancient India, Ariel Woodbury

Children's Book and Media Review

Elephant's friend Dog is sold away and Elephant mourns until the king returns Dog to him. The scrawny tiger tricks a greedy man to cross the river for a gold bangle, but then eats him. The wise little parrot tricks the cat so that he won't eat her babies who are learning to fly. The fishermen catch two large fish who believes in fate, but the wise fish and the clever fish escape. The foolish lion is tricked into jumping down a well. The golden swan's kindness is repaid with greed. The crocodile is a disloyal friend and the monkey …

The Biogenesis Pathway Of Trna-Derived Pirnas In Bombyx Germ Cells., Shozo Honda, Takuya Kawamura, Phillipe Loher, Keisuke Morichika, Isidore Rigoutsos, Yohei Kirino, Phd

Computational Medicine Center Faculty Papers

Transfer RNAs (tRNAs) function in translational machinery and further serves as a source of short non-coding RNAs (ncRNAs). tRNA-derived ncRNAs show differential expression profiles and play roles in many biological processes beyond translation. Molecular mechanisms that shape and regulate their expression profiles are largely unknown. Here, we report the mechanism of biogenesis for tRNA-derived Piwi-interacting RNAs (td-piRNAs) expressed in Bombyx BmN4 cells. In the cells, two cytoplasmic tRNA species, tRNAAspGUC and tRNAHisGUG, served as major sources for td-piRNAs, which were derived from the 5'-part of the respective tRNAs. cP-RNA-seq identified the two tRNAs as major substrates for the 5'-tRNA halves …

Activating Transcription Factor 3 Promotes Loss Of The Acinar Cell Phenotype In Response To Cerulein-Induced Pancreatitis In Mice, Elena N Fazio, Claire C Young, Jelena Toma, Michael Levy, Kurt R Berger, Charis L Johnson, Rashid Mehmood, Patrick Swan, Alphonse Chu, Sean P Cregan, F Jeffrey Dilworth, Christopher J Howlett, Christopher L Pin

Paediatrics Publications

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. …

The Activity Of The Serotonin Receptor 2c Is Regulated By Alternative Splicing, Stefan Stamm, Samuel B. Gruber, Alexander G. Rabchevsky, Ronald B. Emeson

Molecular and Cellular Biochemistry Faculty Publications

The central nervous system-specific serotonin receptor 2C (5HT2C) controls key physiological functions, such as food intake, anxiety, and motoneuron activity. Its deregulation is involved in depression, suicidal behavior, and spasticity, making it the target for antipsychotic drugs, appetite controlling substances, and possibly anti-spasm agents. Through alternative pre-mRNA splicing and RNA editing, the 5HT2C gene generates at least 33 mRNA isoforms encoding 25 proteins. The 5HT2C is a G-protein coupled receptor that signals through phospholipase C, influencing the expression of immediate/early genes like c-fos. Most 5HT2C isoforms show constitutive activity, i.e., signal without ligand binding. The constitutive activity of 5HT2C is …

Sodium Homeostasis In Chronic Kidney Disease, Vivek Soi, Jerry Yee

Nephrology Articles

The pathologic consequences of sodium retention in the CKD population can lead to hypertension, edema, and progressive disease. Sodium excess is responsible for increases in oxidative stress, which alters kidney vasculature. As progression of CKD occurs, hyperfiltration by remaining nephrons compensates for an overall decrease in the filtered load of sodium. In the later stages of CKD, compensatory mechanisms are overcome and volume overload ensues. Nephrotic syndrome as it relates to sodium handling involves a different pathophysiology despite a common phenotype. Extrarenal sodium buffering is also examined as it has significant implications in the setting of advanced CKD.

Probing The Metabolic Phenotype Of Breast Cancer Cells By Multiple Tracer Stable Isotope Resolved Metabolomics, Andrew N. Lane, Julie Tan, Yali Wang, Jun Yan, Richard M. Higashi, Teresa W. -M. Fan

Center for Environmental and Systems Biochemistry Faculty Publications

Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using ¹³C₆-glucose, ¹³C-1+2-glucose, ¹³C₅,¹⁵N₂-Gln, ¹³C₃-glycerol, and ¹³C₈-octanoate as tracers. These tracers were designed to probe the central energy producing …

The Rna-Binding Protein Hur Contributes To Neuroinflammation By Promoting C-C Chemokine Receptor 6 (Ccr6) Expression On Th17 Cells., Jing Chen, Jennifer L. Martindale, Carole Cramer, Myriam Gorospe, Ulus Atasoy, Paul D. Drew, Shiguang Yu

Department of Neurology Faculty Papers

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA …

Reduced Ability Of Calcitriol To Promote Augmented Dopamine Release In The Lesioned Striatum Of Aged Rats, Wayne A. Cass, Laura E. Peters

Neuroscience Faculty Publications

Parkinson’s disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models of PD. However, as PD usually affects older individuals, the ability of calcitriol to promote dopaminergic recovery was examined in lesioned young adult (4 month old), middle-aged (14 month old) and aged (22 month old) rats. Animals were given a single injection of 12 μg 6-OHDA into the right striatum. Four weeks later they were …

N-Acetylcysteine Reduces Cocaine-Cue Attentional Bias And Differentially Alters Cocaine Self-Administration Based On Dosing Order, B. Levi Bolin, Joseph L. Alcorn Iii, Joshua A. Lile, Craig R. Rush, Abner O. Rayapati, Lon R. Hays, William W. Stoops

Behavioral Science Faculty Publications

Background—Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans.

Methods—The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400 mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60 mg). Fourteen individuals …