34. Effects of Adolescent Exposure to Methylphenidate and Amphetamine on Conditioned Place Preference in Adulthood

There is a steady increase in prescription misuse and abuse of ADHD medications in adolescence. Adolescence is a time of continued, but sexually dimorphic, brain maturation, especially in the mesocorticolimbic dopaminergic pathways. Since ADHD medications directly affect these pathways, exposure to them may cause neural alterations manifested as long-term behavioral alterations in adulthood. In previous studies, our lab uncovered drug by sex effects in adult behavioral cross-sensitization after adolescent methylphenidate (MPD) or amphetamine (AMPH) exposure. Behavioral sensitization is a hallmark of neuroplasticity, while conditioned place preference (CPP) directly assesses shifting reward values and neuroplasticity. We hypothesize that adolescent exposure to MPD and AMPH during early adolescence will induce drug- and sex-specific effects in CPP in adulthood, indicative of alterations in the rewarding value of future drug use. Adolescent male and female C57Bl/6J mice (n = 72) received daily i.p. injections of 1mg/kg AMPH, 10mg/kg MPD, or saline. In adulthood, place preference was induced to 1mg/kg METH over 10 days to establish a pairing between the drug and a distinct environment. Increases in time spent in the drug-paired environment at post conditioning in the absence of the drug demonstrates CPP, while subsequent measurements of CPP assess the extinction and strength of this learned association towards a model of relapse susceptibility. Preliminary results suggest adolescent drug exposure by sex interaction effects on both the establishment of and extinction of CPP. These data will determine the extent of shifting reward values of stimulant drugs after abusive, adolescent ADHD drug exposures

34. Effects of Adolescent Methylphenidate Exposure on Susceptibility to Drug Abuse in Adulthood

Methylphenidate (MPD) ,the active ingredient in RitalinTM, is a prescription ADHD stimulant. MPD increases levels of dopamine in the synaptic cleft leading to changes with movement and reward processing. Given the importance of dopamine signaling during developmental critical windows, this study explores neurobiobehavioral alterations resulting from adolescent MPD exposure using conditioned place preference (CPP) and behavioral sensitization paradigms. CPP involves the development of drug-paired associations to environmental features while sensitization tracks motor output in an open field chamber (OFC) that is heightened as a result of chronic stimulant exposure. Behavioral sensitization and CPP indicate underlying neural circuitry changes and are hallmarks of addiction and future drug susceptibility. We hypothesize that adolescent MPD exposure will induce CPP sensitization indicating an increased susceptibility to future drug use. We also hypothesize that adolescent exposure to MPD will produce sexually dimorphic responses. Adolescent mice began the CPP paradigm with habituation on (postnatal day(P22-23)), pre-conditioning (P24-25), conditioning (P26-30), and testing for drug-pair chamber preferences (P31). On P90 the persistence of drug-paired chamber associations will be assessed using a second CPP test. On P91, the persistence of sensitization to stimulant drugs using the OFC will also be assessed. This study shows neurological changes in adolescents will sustain into adulthood. These changes also contribute to a female specific cross sensitization to Methamphetamine. Clinical implications include a possibility of discontinuing MPD prescriptions to females due to increased sensitization or reducing prescription rates of medications containing MPD to adolescents until major developmental changes have all occurred successfully

Doctor of Philosophy

dissertationProteoglycans (PGs), a special class of gly coconjugates, which decorate the outer surface of mammalian cells, consist of a core protein and several glycosaminoglycan (GAG) side chains. PGs regulate many important biological processes, such as fertilization, cell-cell communication, immune defense, anticoagulation, angiogenesis, axon guidance, and many more. Controlling the fine structures of endogenous GAG chains or modulating expression levels of GAG chains can significantly impact many biological processes. However, very little is known about the factors that regulate PG biosynthesis. In this thesis work, chemical probes were designed and synthesized to understand biosynthetic pathways, structures, and functions of PGs. A library of xylosides with different aglycone groups was synthesized using "click chemistry" to stimulate and inhibit GAG production in vitro. These molecular probes serve as excellent tools to unravel the biological significance of PGs and GAG multivalency in many biological systems and lead to the discovery of drugs to treat human disorders/diseases that are associated with aberrant PG structures

Representation of Food and Feasting in Seventeenth-Century Dutch Pronkstillevens (1640-1672)

This study investigates the meaning of foods in pronkstillevens and the reasons for their appeal to mid-seventeenth-century beholders based on both primary and secondary sources. While Svetlana Alpers argued that still lifes evoked visual pleasure, Eddy de Jongh pointed out their hidden symbolism. Pronkstillevens also offered cultural insights and reflected socio-economic conditions of seventeenth-century Netherlands. Julie Berger Hochstrasser claimed that the primacy of Dutch trade was a key to understanding Dutch still life. The major finding of this research is that pronkstillevens were captivating, especially for a mercantile class, because of their exquisite lifelikeness, the representation of admirable affluence and the association to powerful commerce

Functionally Magnetic Gradient Copper-Nickel Material Fabricated via Directed Energy Deposition

Functionally gradient materials (FGMs) of CuSn10 and Inconel 718 were fabricated via a hybrid directed energy deposition (DED) system. The objective of the present thesis is to determine the feasibility of manufacturing CuSn10 and Inconel 718 FGMs via DED and investigate the physical and mechanical properties and the microstructures of the resulting FGMs. The physical tests comprised of conductivity and Seebeck coefficient measurements. The microstructure analysis and mechanical testing include microscopic imaging, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and hardness test. In addition, compressive strength test was performed to analyze the interface bonding behaviors

Multi-Wavelength Properties of Barred Galaxies in the Local Universe. I: Virgo Cluster

We study in detail how the barred galaxy fraction varies as a function of luminosity, HI gas mass, morphology and color in the Virgo cluster in order to provide a well defined, statistically robust measurement of the bar fraction in the local universe spanning a wide range in luminosity (factor of ~100) and HI gas mass. We combine multiple public data-sets (UKIDSS near-infrared imaging, ALFALFA HI gas masses, GOLDMine photometry). After excluding highly inclined systems, we define three samples where galaxies are selected by their B-band luminosity, H-band luminosity, and HI gas mass. We visually assign bars using the high resolution H-band imaging from UKIDSS. When all morphologies are included, the barred fraction is ~17-24% while for morphologically selected discs, we find that the barred fraction in Virgo is ~29-34%: it does not depend strongly on how the sample is defined and does not show variations with luminosity or HI gas mass. The barred fraction depends most strongly on the morphological composition of the sample: when the disc populations are separated into lenticulars (S0--S0/a), early-type spirals (Sa--Sb), and late-type spirals (Sbc--Sm), we find that the early-type spirals have a higher barred fraction (~45-50%) compared to the lenticulars and late-type spirals (~22-36%). This difference may be due to the higher baryon fraction of early-type discs which makes them more susceptible to bar instabilities. We do not find any evidence of barred galaxies being preferentially blue.Comment: 13 pages, 14 figures. Submitted to Ap

Ultrasonography of a Helical Left Common Carotid Artery

Case Presentation: An 83-year-old woman was admitted to the intensive care unit for septic shock at which point an internal jugular central venous line was placed. The patient’s common carotid artery was visualized in an atypical location, lateral to the internal jugular vein. Further inspection revealed the common carotid artery travelling in a rotational trajectory around the internal jugular vein.Discussion: For at least two decades, point-of-care ultrasound has become the standard of care for placing central venous lines. This surprising anatomical orientation is rare and cautions physicians to fully explore a patient’s anatomy prior to placing central lines