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Theses/Dissertations

2009

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Full-Text Articles in Life Sciences

In Silico Prediction Of Non-Coding Rnas Using Supervised Learning And Feature Ranking Methods, Stephen J. Griesmer Dec 2009

In Silico Prediction Of Non-Coding Rnas Using Supervised Learning And Feature Ranking Methods, Stephen J. Griesmer

Theses

This thesis presents a novel method, RNAMultifold, for development of a non-coding RNA (ncRNA) classification model based on features derived from folding the consensus sequence of multiple sequence alignments using different folding programs: RNAalifold, CentroidFold, and RSpredict. The method ranks these folding features according to a Class Separation Measure (CSM) that quantifies the ability of the features to differentiate between samples from positive and negative test sets. The set of top-ranked features is then used to construct classification models: Naive Bayes, Fisher Linear Discriminant, and Support Vector Machine (SVM). These models are compared to the performance of the same models ...


Role And Regulation Of The Actin-Regulatory Protein Hs1 In Tcr Signaling, Esteban Carrizosa Dec 2009

Role And Regulation Of The Actin-Regulatory Protein Hs1 In Tcr Signaling, Esteban Carrizosa

Publicly Accessible Penn Dissertations

Numerous aspects of T cell function, including TCR signaling, migration, and execution of effector functions, depend on the actin cytoskeleton. Cytoskeletal rearrangements are driven by the action of actin-regulatory proteins, which promote or antagonize the assembly of actin filaments in response to external cues. In this work, we have examined the regulation and function of HS1, a poorly-understood actin regulatory protein, in T cells. This protein, which becomes tyrosine phosphorylated upon T cell activation, is thought to function primarily by stabilizing existing branched actin filaments. Loss of HS1 results in unstable actin responses upon TCR engagement and defective Ca2+ responses ...


The Evolutionary Genetics Of Life History In Drosophila Melanogaster, Annalise B. Paaby Dec 2009

The Evolutionary Genetics Of Life History In Drosophila Melanogaster, Annalise B. Paaby

Publicly Accessible Penn Dissertations

Life history traits are critical components of fitness and frequently reflect adaptive responses to environmental pressures. Natural populations of Drosophila melanogaster exhibit patterns of lifespan, fecundity, development time, body size and stress resistance that vary predictably along environmental gradients. Artificial selection studies, genetic correlation analyses, and quantitative trait mapping efforts have demonstrated a genetic basis for the observed phenotypic variation, but few genes have been identified that contribute to natural life history variation. This work employs a candidate gene approach to discover genes and specific polymorphisms that contribute to genetic variance for D. melanogaster life history. Three aging genes, which ...


Effect Of Hydration And Macromolecular Crowding On Peptide Conformation, Aggregation And Folding Kinetics, Smita Mukherjee Dec 2009

Effect Of Hydration And Macromolecular Crowding On Peptide Conformation, Aggregation And Folding Kinetics, Smita Mukherjee

Publicly Accessible Penn Dissertations

Protein folding/misfolding in vivo takes place in a highly crowded and confined environment. Such crowded environment can possibly lead to fewer water molecules surrounding a protein of interest than that seen under in vitro conditions wherein typically dilute aqueous solutions are used. When considering the aforesaid cellular characteristics, such as water depletion and macromolecular crowding; it is reasonable to assume that proteins may experience different energy landscapes when folding in vivo than in vitro. Therefore, we have investigated how degrees of hydration and macromolecular crowding affect the conformation, aggregation and folding kinetics of short peptides.

In order to modulate ...


Cellular And Molecular Analyses Of Neural And Synaptic Development In Zebrafish, Yuanquan Song Dec 2009

Cellular And Molecular Analyses Of Neural And Synaptic Development In Zebrafish, Yuanquan Song

Publicly Accessible Penn Dissertations

Proper function of the nervous system requires the precise wiring of neuronal circuitry, which is established during development via mechanisms that guide cells to establish a correct identity, direct axons to navigate to and make synaptic connections with appropriate targets, and establish and maintain the function of synaptic circuits. Dysfunction of genes implicated in one or more of these processes has been linked to human neurological disorders with behavioral and cognitive manifestations. However, our understanding of how specific gene defects affect circuitry formation, function and in turn behavior remains fragmentary.

I have used zebrafish as a genetic model system to ...


Structural Studies Of Large Integral Membrane Proteins In Reverse Micelles By Solution Nuclear Magnetic Resonance, Joseph Kielec Dec 2009

Structural Studies Of Large Integral Membrane Proteins In Reverse Micelles By Solution Nuclear Magnetic Resonance, Joseph Kielec

Publicly Accessible Penn Dissertations

The structural characterization of integral membrane proteins represents one of the many challenges of the post-genomic era. While membrane proteins comprise approximately 50% of current and potential drug targets, their structural characterization lags far behind that of soluble proteins. Nuclear magnetic resonance (NMR) offers tremendous potential for the investigation of membrane proteins in aqueous environments with respect to structural characterization, relaxation properties, and the details of small ligand interactions. However, the size limitations of solution NMR due to the slow tumbling problem have restricted comprehensive structural characterization of membrane protein NMR structures to the relatively small β-barrel proteins or helical ...


Sensorimotor Integration An A Small Motor Circuit, Nicholas D. Delong Dec 2009

Sensorimotor Integration An A Small Motor Circuit, Nicholas D. Delong

Publicly Accessible Penn Dissertations

Rhythmic motor patterns, which underlie behaviors such as mastication, respiration and locomotion, are generated by specialized neural circuits called central pattern generators (CPGs). Although CPGs can generate their rhythmic motor output in the absence of rhythmic input, these motor patterns are modified by rhythmic sensory feedback in vivo. Furthermore, although the importance of sensory feedback in shaping CPG output is well known, most systems lack the experimental access needed to elucidate the mechanisms underlying sensorimotor integration at the cellular and synaptic level. I am therefore examining this issue using the gastric mill CPG, a circuit which generates the rhythmic retraction ...


Defining A T Cell-Intrinsic Role For Myd88 During Lcmv Infection, Adeeb H. Rahman Dec 2009

Defining A T Cell-Intrinsic Role For Myd88 During Lcmv Infection, Adeeb H. Rahman

Publicly Accessible Penn Dissertations

Immune activation through Toll-like receptors (TLRs) has historically been considered to be a characteristic of cells of the innate, rather than adaptive immune system. Recent studies have challenged this paradigm by demonstrating that TLRs are also expressed on T lymphocytes and that TLR ligands can directly co-stimulate T cell responses in vitro. However, the physiological relevance of these findings during in vivo immune responses was unclear. Mice lacking the critical TLR-adapter protein, myeloid differentiation protein 88 (MyD88), have increased susceptibility to numerous pathogens, highlighting the importance of TLRs in host defense. While the immune impairments associated with MyD88-deficiency have generally ...


Transcriptional And Translational Control Of Zebrafish Mesodermal Development, Lisa L. Chang Dec 2009

Transcriptional And Translational Control Of Zebrafish Mesodermal Development, Lisa L. Chang

Publicly Accessible Penn Dissertations

Establishment of the mesodermal germ layer is a process dependent on the integration of multiple transcriptional and signaling inputs. Here I investigate the role of the transcription factor FoxD3 in zebrafish mesodermal development. FoxD3 gain-of-function results in dorsal mesoderm expansion and body axis dorsalization. FoxD3 knockdown results in axial defects similar to Nodal loss-of-function, and was rescued by Nodal pathway activation. In Nodal mutants, FoxD3 did not rescue mesodermal or axial defects. Therefore, FoxD3 functions through the Nodal pathway and is essential for dorsal mesoderm formation. The FoxD3 mutant, sym1, previously described as a null mutation with neural crest defects ...


Using Evolutionary Genomics To Elucidate Parasite Biology And Host-Pathogen Interactions, Lucia Peixoto Dec 2009

Using Evolutionary Genomics To Elucidate Parasite Biology And Host-Pathogen Interactions, Lucia Peixoto

Publicly Accessible Penn Dissertations

This dissertation exploits phylogenomic approaches to identify genes and gene families likely to be important in the biology of apicomplexan parasites, including Plasmodium (the causative agent of malaria) and Toxoplasma (a leading source of congenital neurological birth defects, and a prominent opportunistic infection in immunosuppressed individuals). In particular, we have explored the significance of lateral gene transfer and gene duplication as sources of evolutionary novelty . Genomic-scale phylogenetic tree comparison identifies surprisingly extensive lateral gene transfer (LGT), including plant-like genes presumably acquired from the algal source of the apicomplexan plastid (apicoplast), and animal-like genes that may have been acquired from these ...


Modular Organization And Composability Of Rna, Miler T. Lee Dec 2009

Modular Organization And Composability Of Rna, Miler T. Lee

Publicly Accessible Penn Dissertations

Life is organized. Organization is largely achieved via composability -- that at some level of abstraction, a system consists of smaller parts that serve as building blocks -- and modularity -- the tendency for these blocks to be independent units that recombine to form functionally different systems. Here, we explore the organization, composition, and modularity of ribonucleic acid (RNA) molecules, biopolymers that adopt three-dimensional structures according to their specific nucleotide sequence. We address three themes: the efficacy of specific sequences to function as modules or as the context in which modules are inserted; the sources of novel modules in modern genomes; and the ...


Roles Of The Ion Channel Nalcn In Neuronal Excitability Control, Boxun Lu Dec 2009

Roles Of The Ion Channel Nalcn In Neuronal Excitability Control, Boxun Lu

Publicly Accessible Penn Dissertations

The resting membrane potential (RMP) of a neuron is set by a complex balance between charged ions, ion channels and transporters. Many of the ion channels have been identified at the molecular level. Missing from the molecular identification has been the voltage-insensitive background sodium ‘‘leak’’ conductance that depolarizes the RMP from the equilibrium potential of potassium and provides a crucial contribution to neuronal excitability

One candidate for the molecular identity of this conductance is the protein NALCN. NALCN is a previously uncharacterized orphan member in the sodium/calcium channel family. It is widely expressed in the nervous system. My thesis ...


Mechanisms Of Notch-Mediated Inhibition Of Skeletal Myogenesis, Matthew F. Buas Dec 2009

Mechanisms Of Notch-Mediated Inhibition Of Skeletal Myogenesis, Matthew F. Buas

Publicly Accessible Penn Dissertations

The Notch pathway is an evolutionarily conserved signaling cascade that regulates many cell fate decisions. Recent work has revealed that Notch plays critical roles in the control of skeletal muscle development and regeneration. In the embryo, Notch maintains a pool of myogenic progenitor cells and prevents their premature differentiation. In the adult, after muscle injury, Notch signaling is essential for the initial expansion of muscle stem cells, or satellite cells.

While it has been known for over a decade that Notch activity represses myogenic differentiation, the molecular mechanisms by which this inhibition occurs are poorly defined. In this thesis, I ...


Niche Partitioning Among Arbuscular Mycorrhizal Fungi And Consequences For Host Plant Performance, Jennifer H. Doherty Dec 2009

Niche Partitioning Among Arbuscular Mycorrhizal Fungi And Consequences For Host Plant Performance, Jennifer H. Doherty

Publicly Accessible Penn Dissertations

We understand little about the factors that determine and maintain local species diversity of arbuscular mycorrhizal fungi (AMF), the reasons why a single plant has multiple AMF partners, and how that diversity influences host plant performance. The extent to which co-occurring AMF species occupy different niche space, based on their ability to tolerate different soil conditions or differentially promote host plant growth in those differing conditions, offers possible explanations for the maintenance of diversity.

AMF community composition was examined in relation to soil variability in a naturally metalliferous serpentine grassland and along a Cu, Cd, Pb, and Zn soil contamination ...


Evolution Of Genome-Wide Gene Regulation In The Budding Yeast Cell-Division Cycle, Daniel F. Simola Dec 2009

Evolution Of Genome-Wide Gene Regulation In The Budding Yeast Cell-Division Cycle, Daniel F. Simola

Publicly Accessible Penn Dissertations

Genome-wide regulation of gene expression involves a dynamic epigenetic structure which generates an organism's life-cycle. Although changes in gene expression during development have broad effects on many basic phenomena including cell growth, differentiation, morphogenesis, and disease progression, the evolutionary forces influencing gene expression dynamics and gene regulation remain largely unknown, due to the nature of gene expression as a polygenic, quantitative trait. Moreover, gene expression is regulated differentially over time, so evolutionary forces may be influenced by developmental context. To advance the understanding of evolution in the context of the life-cycle, the architecture of gene expression timing control and ...


Genetic Structure Of Yonahlossee Salamander Populations., Joshua Andrew Rudd Dec 2009

Genetic Structure Of Yonahlossee Salamander Populations., Joshua Andrew Rudd

Electronic Theses and Dissertations

Plethodon yonahlossee is the largest eastern Plethodontid salamander. It has been classified as a species of greatest conservation need by the Tennessee Wildlife Resources Agency (TWRA). Found only in mountainous areas along the borders of Tennessee, North Carolina, and Virginia, populations of the yonahlossee are considered to be rare and local throughout their range. Genetic differentiation among populations of any species is usually attributable to long-standing, extrinsic barriers to gene flow. Because of their disjunct population structure and some observed morphological variation, genetic differentiation among yonahlossee populations is expected. A genetic structure study of yonahlossee was conducted to identify any ...


Investigating Nectar Rhythms In Squash (Cucurbita Pepo): Effects On Honey Bee (Apis Mellifera) Foraging Behavior., Samuel David Boyd Dec 2009

Investigating Nectar Rhythms In Squash (Cucurbita Pepo): Effects On Honey Bee (Apis Mellifera) Foraging Behavior., Samuel David Boyd

Electronic Theses and Dissertations

Experiments were performed to investigate the influence of water availability on the diel patterns of nectar secretion (volume, concentration, sugar production) in male squash flowers as well as to discover what physical component of nectar honey bees use to trigger their time-memory. Squash plants were grown in the greenhouse and in the field under both constant and variable watering regimes. Throughout anthesis, nectar volume and sugar concentration were recorded. In the field, the temporal distribution of arrivals to squash was observed with and without blossoms present. In the greenhouse and in the field, squash flowers exhibit a consistent diel pattern ...


Reproductive Success Of American Kestrels (Falco Sparverius) Nesting In Boxes Along An Interstate In Northeastern Tennessee., Jennifer Robertson Powers Dec 2009

Reproductive Success Of American Kestrels (Falco Sparverius) Nesting In Boxes Along An Interstate In Northeastern Tennessee., Jennifer Robertson Powers

Electronic Theses and Dissertations

Nest box programs provide supplemental nest sites for American Kestrels, Falco sparverius. When the availability of nest sites is a limiting factor, the addition of nest boxes can increase local breeding populations. These programs also facilitate the collection of data on breeding kestrels.

This study focuses on an American Kestrel (Falco sparverius) nest box trail along Interstate 26 in northeastern Tennessee during the breeding seasons of 1998, 1999, 2000, 2003, 2004, 2006, and 2009. Productivity measures and reproductive success of nesting birds are provided and compared to other programs. The data are analyzed across years and by box. Finally, a ...


Dopamine D2 Receptor Priming Enhances Dopaminergic Response To Amphetamine In The Nucleus Accumbens: Role Of The D1 And D2 Receptors., Kimberly Norris Huggins Dec 2009

Dopamine D2 Receptor Priming Enhances Dopaminergic Response To Amphetamine In The Nucleus Accumbens: Role Of The D1 And D2 Receptors., Kimberly Norris Huggins

Electronic Theses and Dissertations

In past work, we have shown neonatal quinpirole (dopamine D2/D3 agonist) treatment produces a significant increase in dopamine D2 receptor sensitivity, a phenomenon known as D2 receptor priming. Dopamine D2 receptor priming is common in psychosis. Male and female rats were administered quinpirole (1mg/kg) or saline from postnatal days 1-11 and raised to adulthood (P60). As adults, rats were administered d-amphetamine sulfate (1mg/kg) or saline every other day for 14 days. Approximately 10 min before each amphetamine or saline injection, animals were administered the D1 antagonist SCH 23390 (0.1 mg/kg ...


Influence Of Soil Water Repellency On Post-Fire Revegetation Success And Management Techniques To Improve Establishment Of Desired Species, Matthew D. Madsen Dec 2009

Influence Of Soil Water Repellency On Post-Fire Revegetation Success And Management Techniques To Improve Establishment Of Desired Species, Matthew D. Madsen

Theses and Dissertations

The influence of soil water repellency (WR) on vegetation recovery after a fire is poorly understood. This dissertation presents strategies to broaden opportunities for enhanced post-fire rangeland restoration and monitoring of burned piñon and juniper (P-J) woodlands by: 1) mapping the extent and severity of critical and subcritical WR, 2) determining the influence of WR on soil ecohydrologic properties and revegetation success, and 3) evaluating the suitability of a wetting agent composed of alkylpolyglycoside-ethylene oxide/propylene oxide block copolymers as a post-fire restoration tool for ameliorating the effects of soil WR and increasing seedling establishment. Results indicate that:

• Post-fire patterns ...


Inferring Dispersal Of Aquatic Invertebrates From Genetic Variation: A Comparative Study Of An Amphipod (Talitridae Hyalella Azteca) And Mayfly (Baetidae Callibaetis Americanus) In Great Basin Springs, Heather Lynn Stutz Dec 2009

Inferring Dispersal Of Aquatic Invertebrates From Genetic Variation: A Comparative Study Of An Amphipod (Talitridae Hyalella Azteca) And Mayfly (Baetidae Callibaetis Americanus) In Great Basin Springs, Heather Lynn Stutz

Theses and Dissertations

Whether active or passive, dispersal accompanied by gene flow shapes the population genetics and evolutionary divergence of species. Indirect methods which use genetic markers have the ability to assess effective dispersal—that which resulted in gene flow. My objective was to see if an aquatic insect and an obligate aquatic invertebrate show similar phylogeographic patterns and genetic uniqueness. Hyalella azteca and Callibaetis americanus were collected from 4-5 springs in each of six basins in the Great Basin of western North America. No dispersal or genetic studies of C. americanus have been conducted to date. However, several studies focusing on mtDNA ...


Shortest Geometric Paths Analysis In Structural Biology, Ryan G. Coleman Dec 2009

Shortest Geometric Paths Analysis In Structural Biology, Ryan G. Coleman

Publicly Accessible Penn Dissertations

The surface of a macromolecule, such as a protein, represents the contact point of any interaction that molecule has with solvent, ions, small molecules or other macromolecules. Analyzing the surface of macromolecules has a rich history but analyzing the distances from this surface to other surfaces or volumes has not been extensively explored. Many important questions can be answered quantitatively through these analyses. These include: what is the depth of a pocket or groove on the surface? what is the overall depth of the protein? how deeply are atoms buried from the surface? where are the tunnels in a protein ...


Environmental Nickel And Arabidopsis Thaliana: Accumulation, Localization, And The Effect Of Propagation On A Nickel-Free Medium, Gabriel Mark Fickett Dec 2009

Environmental Nickel And Arabidopsis Thaliana: Accumulation, Localization, And The Effect Of Propagation On A Nickel-Free Medium, Gabriel Mark Fickett

Honors Projects and Presentations: Undergraduate

Many heavy metals, including nickel, are vitally important to plant species at very low concentrations in the environment, but become quite toxic when present in higher concentrations (Kovalchuk et al. 2001). Nickel is vital in small amounts to plants because it is used in some enzymatic reactions as a co-factor (Mizuno et al. 2005). Most notably, nickel is a necessary component of ureases in higher plants and therefore necessary for nitrogen metabolism (Brown et al. 1990).


The Effects Of Different Doses Of Caffeine On A 40 Kilometer Cycling Time Trial: A Dose-Response Study, Michael Martin Dec 2009

The Effects Of Different Doses Of Caffeine On A 40 Kilometer Cycling Time Trial: A Dose-Response Study, Michael Martin

Masters Theses

Abstract The purpose of this study was to determine the ergogenic response to different caffeine doses of 3 mg/kg and 6 mg/kg consumed by trained cyclists 1 hour prior to a 40 kilometer cycling time trial. It was hypothesized that there would not be a difference in time trial performance following caffeine supplementation of a 3 mg/kg dose as compared to a 6 mg/kg dose. Sixteen male subjects, age 18-40, were initially assessed via a VO2max test on an indoor cycle trainer. Subjects then reported to the lab on 4 separate occasions following a 10 hour ...


The Effect Of Heavy Handrail Support On Blood Pressure Response In Normotensive Adults During Treadmill Walking, Kevin Brian Reid Dec 2009

The Effect Of Heavy Handrail Support On Blood Pressure Response In Normotensive Adults During Treadmill Walking, Kevin Brian Reid

Masters Theses

Physiological and hemodynamic responses to handrail support during treadmill walking have shown a blunted response when compared to non-handrail support. The effects of treadmill walking, with the inclusion of “heavy” upper limb and torso activation through handrail support is yet unreported. The effect of “heavy” support through side handrail support (SHRS) and front console support (C) versus no handrail support (NHRS) treadmill walking was studied utilizing both slow/low (2.5 mph & 3% elevation) and high/fast (3.5 mph & 11% elevation) energy expenditure levels. Seventeen healthy adults (43.89 +/- 6.07 years) completed trials at both energy expenditure levels ...


Comparison Of Single-Use And Multiple-Use Electrodes For Sensory, Motor Threshold Amplitudes And Force Production, Lucia Maloy Dec 2009

Comparison Of Single-Use And Multiple-Use Electrodes For Sensory, Motor Threshold Amplitudes And Force Production, Lucia Maloy

Theses and Dissertations

Context: Electrodes play an important role in interfacing tissue with electrical stimulation devices. Manufacturers recommend that adhesive metallic mesh cloth electrodes be used no more than 10 times before they are discarded, however, clinically the electrodes are often used up to 30 times. Another concern is sanitation. When electrodes are used on different patients, there is a chance for cross-contamination and bacterial growth on the electrode. Objective: To compare amplitudes of perceived sensation, motor twitch and force produced at specific amplitudes using single-use electrodes that run no risk of cross-contamination, and multiple-use electrodes. Design: Mixed model ANOVA with the subject ...


Progress Toward The Total Synthesis Of Lyconadin A, Yu Zhang Dec 2009

Progress Toward The Total Synthesis Of Lyconadin A, Yu Zhang

Theses and Dissertations

Lyconadin A is a pentacyclic Lycopodium alkaloid isolated from the club moss Lycopodium complanatum with antitumor properties. We have developed a novel 7-exo/6-exo acyl radical cascade cyclization as a method of making the bicyclo[5.4.0]undecane ring system of lyconadin A. The model products are trans-fused ring systems, while a cis-fused ring system is needed in lyconadin A. We have discovered a method to convert the trans-fused model cascade cyclization product into the desired cis isomer. Based on Donohoe's pyridone synthesis, we developed a method for the construction of 5-alkyl and ...


The Ecological Importance Of Extrinsic And Intrinsic Drivers Of Animal Movement, Josh Earl Rasmussen Dec 2009

The Ecological Importance Of Extrinsic And Intrinsic Drivers Of Animal Movement, Josh Earl Rasmussen

Theses and Dissertations

The movement of individuals is foundational to many ecological processes. For example, the movement of an organism from one place to another alters population density at both sites and has potential for affecting the genetic dynamics within the new population. Individual movement events may be in synchrony with overall trends in populations, e.g. spawning migrations, or may be atypical (asynchronous). This latter movement type can affect population and metapopulation dynamics, depending on its prevalence within a population. Nevertheless, given the complexity of interactions, the causative factors of movement are understood vaguely, much less for aquatic organisms. Drivers of movement ...


Influence Of Cardiac Output On Oxygen Uptake Kinetics, Crystelle Kiyoko Grant Dec 2009

Influence Of Cardiac Output On Oxygen Uptake Kinetics, Crystelle Kiyoko Grant

Theses and Dissertations

The purpose of this study was to evaluate increased cardiac output (Q) on oxygen kinetics at exercise intensities above and below the lactate threshold (LT). We hypothesized the increase in Q using head-out water immersion (HOI) while treadmill running would reduce the rate constant of the fast component and reduce the amplitude of the slow component of oxygen kinetics compared with land treadmill running. Subjects (n=10) performed two 6 min exercise bouts at a 15% below and above the LT on a land and underwater treadmill following rest. A single exponential equation [VO2(t) = VO2(b) + A1•(1-e-t/TC1 ...


Cocaine And Mefloquine-Induced Acute Effects In Ventral Tegmental Area Dopamine And Gaba Neurons, David Wilbanks Allison Dec 2009

Cocaine And Mefloquine-Induced Acute Effects In Ventral Tegmental Area Dopamine And Gaba Neurons, David Wilbanks Allison

Theses and Dissertations

The aim of the two studies presented here was to evaluate the effects of cocaine and mefloquine (MFQ) on γ-aminobutyric acid (GABA) and dopamine (DA) neurons in the ventral tegmental area (VTA). Cocaine: In vivo, lower doses of intravenous cocaine (0.25-0.5 mg/kg), or methamphetamine (METH), enhanced VTA GABA neuron firing rate via D2/D5 receptor activation. Higher cocaine doses (1.0-2.0 mg/kg) inhibited their firing rate. Cocaine and lidocaine inhibited the firing rate and spike discharges induced by stimulation of the internal capsule (ICPSDs) at dose levels 0.25-2 mg/kg (IC50 1.2 mg ...