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Full-Text Articles in Physiology

Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias Jun 2014

Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias

Theses and Dissertations

This thesis will be organized into three chapters discussing the mechanism underlying the onset and progression of osteoarthritis (OA) in the temporomandibular joint (TMJ). Understanding the mechanism of OA development in the TMJ helps in understanding how OA progresses and how to treat this disease. The goal of this investigation is to examine the process of cartilage degeneration and OA biomarker expression in the TMJ to understand their role in TMJ OA onset and development.Chapter one covers mechanisms that are altered in TMJ OA during disease progression. Using animal models with different stressors such as mechanical disturbances, direct injury, and …


Rapid Adaptation Of Dopamine D2 Receptor Responses In The Brain And Blood Following Acute Ethanol, Ryan J. Folsom Jun 2014

Rapid Adaptation Of Dopamine D2 Receptor Responses In The Brain And Blood Following Acute Ethanol, Ryan J. Folsom

Theses and Dissertations

Dopamine (DA) D2 receptor expression parallels DA levels in the brain and these autoreceptors have been shown to be modulated by long-term ethanol exposure. We have previously demonstrated that ventral tegmental area (VTA) GABA neurons also express D2 autoreceptors (D2R), and that DA and D2R agonists markedly enhance the excitability of VTA GABA neurons, opposite to their well-known auto-receptor inhibition of DA neurons. Most importantly, D2R antagonists block ethanol inhibition of VTA GABA neurons and D2R expression in VTA GABA neurons down-regulates with chronic ethanol, as others have shown for whole VTA D2R expression. The aim of this study was …


Examination Of Anabolic Signaling And Muscle Growth With Caffeine Treatment In Overloaded Hindlimb Muscle And Electrically Stimulated Muscle Lacking Liver Kinase B1, Timothy Michael Moore Jun 2014

Examination Of Anabolic Signaling And Muscle Growth With Caffeine Treatment In Overloaded Hindlimb Muscle And Electrically Stimulated Muscle Lacking Liver Kinase B1, Timothy Michael Moore

Theses and Dissertations

Skeletal muscle has the ability to increase in size (hypertrophy) after resistance is placed upon it. This hypertrophy is marked by significant upregulation of the mammalian target of rapamycin (mTOR) and its downstream targets. The upstream kinases, protein kinase B (also known as Akt) and AMP-activated protein kinase (AMPK), are two of the many regulators of the mTOR pathway. Recent studies suggest that the widely consumed neuroactive compound caffeine could potentially inhibit mTOR by acting through Akt and/or AMPK. The purpose of this thesis was to: 1) determine if caffeine can inhibit the mTOR pathway and ultimately attenuate skeletal muscle …


Divalent Copper Compounds As Inhibitory Agents Of Influenza A, Nathan Allan Gordon Jun 2014

Divalent Copper Compounds As Inhibitory Agents Of Influenza A, Nathan Allan Gordon

Theses and Dissertations

Influenza A virus (IAV) exhibits a high mutation frequency. Mutations in primary viral targets such as hemagglutinin, neuraminidase, and the proton channel M2 have afforded IAV with substantial drug resistance to previously effective drugs such as oseltamivir and amantadine (AMT) along with their analogs. One of the main drug-resistant alterations in the M2 protein that has become ubiquitous is the mutation S31N. Divalent copper has previously been suggested to have anti-IAV properties using in vitro assays involving Xenopus oocytes and SSNMR. In this work, the EC50 of AMT, two AMT analogs, CuCl2 · 2H2O, and four …


Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden May 2014

Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden

Theses and Dissertations

Receptors for advanced glycation end-products (RAGE) are pattern recognition receptors of the immunoglobulin superfamily highly expressed in the lung. Likely functions include the modulation of pulmonary inflammation during disease. However, the contributions of RAGE in the developing lung in cases where secondhand smoke (SHS) exposure occurs are unknown. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, we exposed gestating dams to a controlled dose of SHS during the last four critical days of in utero lung morphogenesis. We discovered that both maternal and fetal lungs respond to SHS by up-regulating RAGE. Exposed fetuses were markedly …


Synaptic Plasticity In Gabaergic Inhibition Of Vta Neurons, Jennifer Kei Mabey May 2014

Synaptic Plasticity In Gabaergic Inhibition Of Vta Neurons, Jennifer Kei Mabey

Theses and Dissertations

Past research has demonstrated that the motivational effects of opiates causes a change in ventral tegmental area (VTA) γ-amino butyric acid (GABA) subtype A receptor [GABA(A)R] complexes in opiate-dependent animals, which switch from a GABA-induced hyperpolarization of VTA GABA neurons to a GABA-induced depolarization. Previously shown in naïve animals, superfusion of ethanol (IC50 = 30 mM) and the GABA(A)R agonist muscimol (IC50 = 100 nM) decreased VTA GABA neuron firing rate in a dose-dependent manner. The aim of this study was to evaluate VTA GABA neuron excitability, GABA synaptic transmission to VTA GABA neurons, and a potential switch in GABA(A)R …


Cloning The Ultrabithorax Gene In Tribolium Castaneum, Kara I. Ludlow, Dr. Randy Bennett Apr 2014

Cloning The Ultrabithorax Gene In Tribolium Castaneum, Kara I. Ludlow, Dr. Randy Bennett

Journal of Undergraduate Research

My original proposal was to clone the extradenticle gene in Tribolium castaneum (red flour beetle); however, I worked in conjunction with Laura Newell who received an ORCA grant to work with Dr. Bennett cloning the Ultrabithorax gene of the red flour beetle. To further previous research, it was determined that the Ultrabithorax gene needed to be cloned first, so Laura and I worked on that project together. Due to complications and unexpected delays, we were only able to finish cloning the Ultrabithorax gene of the beetle and did not have time to clone the extradenticle gene, as well.


Gpr55: A Potential Enhancer Of Learning And Memory In The Hippocampus, Rachel Schneider, Dr. Jeff Edwards Apr 2014

Gpr55: A Potential Enhancer Of Learning And Memory In The Hippocampus, Rachel Schneider, Dr. Jeff Edwards

Journal of Undergraduate Research

My project goal was to understand how G-protein coupled receptor 55, (GPR55), a novel cellular pathway in the hippocampus, contributes to learning and memory. Recent research of neurodegenerative diseases, particularly Alzheimer’s, has primarily focused on understanding how learning occurs and how memories are encoded within the brain. Understanding the process in a normal brain and then how it is disrupted in a diseased brain is essential to making headway on treatments for neurodegeneration. Some studies have shown that to encode memories, the brain changes neural synapses to either strengthen or weaken the electrical pathways, which is a process known as …


Ceramides, Mitochondrial Fission, And Reactive Oxygen Species, A Novel Mechanism Of Obesity-Induced Insulin Resistance, Braden Tucker, Dr. Benjamin Bikman Apr 2014

Ceramides, Mitochondrial Fission, And Reactive Oxygen Species, A Novel Mechanism Of Obesity-Induced Insulin Resistance, Braden Tucker, Dr. Benjamin Bikman

Journal of Undergraduate Research

With the unabated rise in obesity in the United States and globally (1), increasing efforts are being devoted to understand and prevent both the onset and the consequences of excess fat gain. As evidenced by health trends, efforts to curtail weight gain have proven largely ineffective, as the number of obese adults in the U.S. is projected to grow by 2.4 million annually (2). The increased prevalence of obesity would not be noteworthy if such a trend were not accompanied by a substantial economic and personal cost—medical costs are roughly $150 billion annually and obese individuals may expect a loss …


Histological Validation Of Alzheimer’S Disease And Cerebrovascular Disease Imaging Biomarkers, Brigham Barzee, Brett Gardiner, Dr. Jon Wisco Apr 2014

Histological Validation Of Alzheimer’S Disease And Cerebrovascular Disease Imaging Biomarkers, Brigham Barzee, Brett Gardiner, Dr. Jon Wisco

Journal of Undergraduate Research

The purpose of this study is to analyze spatial co-localizations between amyloid beta (Aβ), tau, and iron in postmortem brains of Alzheimer’s disease (AD) and cerebrovascular disease (CVD) patients. Iron is readily visible in T2* magnetic resonance images (MRI), and has been shown to be spatially correlated with Aβ plaques in AD. Neurofibrillary tangles of tau protein are also associated with AD, and Aβ plaques are also found in the walls of the vessels in CVD. If iron co-localizes with Aβ, then the location of the iron—parenchyma vs. sulci—as seen in MRI could reveal if the disease is possibly AD …


Expression Of Htra1 And Tgfb1 In Osteoarthritis, Karl Andersen, Dr. David Kooyman Apr 2014

Expression Of Htra1 And Tgfb1 In Osteoarthritis, Karl Andersen, Dr. David Kooyman

Journal of Undergraduate Research

Osteoarthritis increasingly debilitates and causes discomfiture to millions of people worldwide. Most people over 65 years of age suffer from symptoms of osteoarthritis. There has, up to this point, been effectively no clear understanding of the processes of the body that contribute genetically or mechanically to this severe condition. The result of this lack of knowledge is a general absence of prevention and treatment measures. As of today, treatments consist only of joint replacement and pain reduction measures.


Computerized Drug Screening Of The S31n Mutant Of The Influenza A Virus, Mitchell Gleed, David D. Busath Apr 2014

Computerized Drug Screening Of The S31n Mutant Of The Influenza A Virus, Mitchell Gleed, David D. Busath

Journal of Undergraduate Research

Influenza is responsible for millions of hospitalizations and deaths every year. Treating the influenza virus has become increasingly difficult since mutant viruses have rendered previously viable drugs ineffective. New drug-screening procedures are now necessary in order to speed up the process of viable drug discovery. Molecular simulations have proven valuable for studying drug effectiveness in wild-type flu viruses, but little has been done on prevailing influenza mutants. Influenza mutants often feature a change in the M2 proton channel, a critical component in the viral replication and infection cycle. To counter this, drugs must be discovered that can block the influenza …


Protein Signaling Effects On Embryonic Limb Formation, Derrick Crawford, Dr. Jeffery Barrow Apr 2014

Protein Signaling Effects On Embryonic Limb Formation, Derrick Crawford, Dr. Jeffery Barrow

Journal of Undergraduate Research

Congenital limb malformations occur in approximately 1 in 500 live births. These defects are due largely because of genetic and developmental causes. In my experiments, I have researched the source of these defects to understand how cell to cell signaling affects digit and limb formation. I was able to manipulate signaling between limb tissues during development to understand better how proteins interact with each other to stimulate growth in chick embryos. These same proteins have been observed in mammals such as mice and hopefully in the future may be applied in human development as well. There are many key factors …


The Role Of Trpv1 In Hippocampal Plasticity, Andrew Wallmann, Dr. Jeff Edwards Apr 2014

The Role Of Trpv1 In Hippocampal Plasticity, Andrew Wallmann, Dr. Jeff Edwards

Journal of Undergraduate Research

Until recently, our understanding of the molecular mechanisms behind memory has been extremely limited. However, recent studies indicate that memory formation is associated with two forms of neuronal plasticity known as long-term potentiation (LTP) and long-term depression (LTD) (Bailey & Kandel, 2008). These are physiological processes that essentially alter the strength of a synapse between two neurons and are of particular importance in the brain region called the hippocampus. The hippocampus is heavily associated with learning and memory and is a frequent target of research for this reason. A novel form of LTP has recently been found within the hippocampus …


Over-Expression Of Age Receptors In The Adult Mouse Lung A New Model For The Study Of Copd, Megan Stogsdill, Dr. Paul Reynolds Apr 2014

Over-Expression Of Age Receptors In The Adult Mouse Lung A New Model For The Study Of Copd, Megan Stogsdill, Dr. Paul Reynolds

Journal of Undergraduate Research

Receptors for advanced glycation end products (RAGE) are receptors that can bind a variety of ligands and are members of the immunoglobin family of cell surface receptors. RAGE is found in many tissue types during inflammatory lesions but is found most abundantly in the lung, where it was subsequently discovered (1). It is known to bind to chemicals found in cigarette smoke (2) and has been implicated as a progression factor in a number of diseases including chronic obstructive pulmonary disease (COPD) (3).


The Distribution Of The Alpha 5 Nachr Subunits In The Mouse Lung, Jason Porter, Dr. Paul Reynolds Apr 2014

The Distribution Of The Alpha 5 Nachr Subunits In The Mouse Lung, Jason Porter, Dr. Paul Reynolds

Journal of Undergraduate Research

The study of developing tissues is extremely important in the field of biology. Each organ in the body adheres to an extremely complex and organized development process involving specific signaling molecules and pathways. Pulmonary development is no exception. Lung development adheres to intimately orchestrated processes that require precisely regulated reciprocal interactions between developing respiratory epithelium and the surrounding splanchnic mesenchyme. Proper lung development involves both spatial and temporal control of a myriad of factors including transcription factors, growth factors, cell surface receptors, and extracellular matrix constituents. My hypothesis when I began this project was that a5 subunits are expressed in …


Aer Signals Outgrowth Of Mesenchyme Cells, Owen Owens, Dr. Jeffery R. Barrow Apr 2014

Aer Signals Outgrowth Of Mesenchyme Cells, Owen Owens, Dr. Jeffery R. Barrow

Journal of Undergraduate Research

The Apical Ectodermal Ridge has been of great interest to those studying the development of the mammalian limb every since it was discovered that the AER is vital to the formation of correct limb patterning and general limb formation. The AER is a ridge of cells located on the tip of the mammalian limb where it signals inner cells, called mesenchyme during development. This study analyzed proliferation, or cell dividing, and apoptosis, or programmed cell death, of mesenchymal cells in the hope to support the hypothesis that the AER signals mesenchymal cells to migrate, not proliferate or undergo apoptosis. We …


Upr Contributes To Osteoarthritis In The Bardet-Biedl Syndrome Mouse Model, David Nolte, Dr. David Kooyman Apr 2014

Upr Contributes To Osteoarthritis In The Bardet-Biedl Syndrome Mouse Model, David Nolte, Dr. David Kooyman

Journal of Undergraduate Research

Osteoarthritis (OA) is the most prevalent form of arthritis, affecting more than 26 million people in the United States1. The condition decreases mobility and causes pain. Furthermore, the spending for medical treatment of osteoarthritis is increasing quickly: Spending doubled from 1994 to 2005. With the increasing age of the U.S. population, prevalence of OA is expected to continue rising1. Thus it is important to find effective treatments to alleviate symptoms and/or prevent osteoarthritis. Recent research has shown that osteoarthritis involves more than just the cartilage of the joint. Synovium and adipose tissue contribute to the breakdown of articular cartilage2. Also, …


Synaptic Plasticity In The Rodent Hippocampus Involvement Of Trpv1 In Plasticity Of Area Ca1, Jared Weed, Dr. Jeffrey Edwards Apr 2014

Synaptic Plasticity In The Rodent Hippocampus Involvement Of Trpv1 In Plasticity Of Area Ca1, Jared Weed, Dr. Jeffrey Edwards

Journal of Undergraduate Research

The hippocampus is the area of the brain where long-term declarative memories are formed. Synaptic plasticity, the long-term strengthening or weakening of the synapse (the connection between two neurons), is the proposed cellular mechanism for the process of memory formation. The two types of synaptic plasticity are long-term potentiation (LTP), in which a synapse becomes strengthened; and long-term depression (LTD), in which a synapse becomes weakened.


Mechanisms In Learning And Memory, Michael Mcneil, Dr. Jeffrey Edwards Apr 2014

Mechanisms In Learning And Memory, Michael Mcneil, Dr. Jeffrey Edwards

Journal of Undergraduate Research

Endocannabinoids are molecules that play an important role in neuromodulation and are also known to be a factor in many peripheral nervous system functions such as appetite and pain sensation. Recent discoveries have also shown that endocannabinoids and their cell-signaling mechanisms are found within the central nervous system, specifically within the hippocampus, an active component of declarative or explicit memory, yet their role in the CNS is largely unknown. Within the hippocampus there are two main categories of neurons, the pyramidal cells and the interneurons, and both are critical for hippocampal function. However, the interneurons appear to be involved in …


Researching The Effects Of Osteoarthritis As A Systemic Immune Response, Danielle Peterson, Dr. David Kooyman Apr 2014

Researching The Effects Of Osteoarthritis As A Systemic Immune Response, Danielle Peterson, Dr. David Kooyman

Journal of Undergraduate Research

Our bodies are dynamic structures that do not operate as individual compartments, but as a whole. When something goes awry in one specific tissue or organ, specific signals from that diseased area are released affect other tissues. I received an ORCA grant last year to study my hypothesis that degradation of Osteoarthritis (OA) is primarily associated with a systemic immune response to trauma of articular cartilage. In order to verify this hypothesis, a treatment that creates OA in one localized area while other tissues remained undamaged was needed. The OA genetic mutant mice that researchers normally turn to couldn’t be …


Localizing Endocannabinoid Receptors Gpr55 And Gpr119 To Subtypes Of Neurons In The Hippocampus, Ryan Williamson, Dr. Jeff Edwards Apr 2014

Localizing Endocannabinoid Receptors Gpr55 And Gpr119 To Subtypes Of Neurons In The Hippocampus, Ryan Williamson, Dr. Jeff Edwards

Journal of Undergraduate Research

The hippocampus is the part of the brain that mediates learning and memory by altering the function of synapses within its circuitry via intracellular signaling molecules. The ability of synapses to change is called synaptic plasticity. Hippocampal synaptic plasticity can be mediated by endogenous lipid-based signaling molecules called endocannabinoids (eCBs) [3]. Two of the best studied eCBs are anandamide (AEA) and 2-arachidonoyl glycerol (2-AG). Physiology data suggests that AEA may mediate synaptic plasticity in neurons of the stratum radiatum region of the hippocampus by binding to an unclassified G protein-coupled receptor called GPR55 [2,3,4,5]. Additionally, another unclassified G-protein coupled receptor, …


The Role Of The Apical Ectodermal Ridge, David Barnes, Dr. Jeffery Barrow Apr 2014

The Role Of The Apical Ectodermal Ridge, David Barnes, Dr. Jeffery Barrow

Journal of Undergraduate Research

Limb formation in tetra pods, animals with four legs, starts with the outgrowth of lateral plate mesoderm at the level of both forelimb and hind limb. A ridge of ectodermal tissue located at the distal margin, named the apical ectodermal ridge (AER), plays an essential role for the outgrowth and patterning of limbs. Patterning is defined as molecular or morphological differences that are established along an axis. The limb is patterned along each of its three axes: along the proximal to distal (PD) axis, the nature of the limb changes from humerus/femur (stylopod) to radius, ulna/tibia, fibula (zeugopod), to hand/foot …


The Nectin-Zyxin Interaction’S Role In Emt, Bradley Scott Colton, Dr. Marc Hansen Apr 2014

The Nectin-Zyxin Interaction’S Role In Emt, Bradley Scott Colton, Dr. Marc Hansen

Journal of Undergraduate Research

The purpose of our experiment was to prove the interactions between three different proteins named nectin, zyxin, and VASP. It is thought that these proteins are involved in forming interactions with the actin cytoskeleton between neighboring cells and add to the cell adhesion between cells in an epithelial layer of cells. Normally cells need to stick together to function together as a layer of cells. One of the characteristics of cancer is when cells break these cell-to-cell adhesions in order to migrate to different areas of the body and set up new tumor sites. This process is known as epithelialmesenchymal …


Rage Expression In Inflammatory Lung Diseases Triggered By Air Pollutants, Tyler Earley, Dr. Paul Reynolds Apr 2014

Rage Expression In Inflammatory Lung Diseases Triggered By Air Pollutants, Tyler Earley, Dr. Paul Reynolds

Journal of Undergraduate Research

I was given a research grant of $1,500. My project was centered around discovery of cellsignaling pathways linked to inflammation specific to the lung. We studied a receptor that may be shown to integrally participate in inflammation in such diseases as COPD and Asthma. My studies followed Receptors for advanced glycation end-products (RAGE) which have been implicated in mechanisms of sustained pulmonary inflammation associated with several pathological conditions. This project sought to investigate the direct interaction of particulate matter and RAGE as well as RAGE’s role in perpetuating an inflammatory response in epithelial cells resident to the respiratory tract. This …


Regulation Of P450scc Expression: Ampk And Cortisol Release, Kimberly Dalton, Dr. Allan Judd Apr 2014

Regulation Of P450scc Expression: Ampk And Cortisol Release, Kimberly Dalton, Dr. Allan Judd

Journal of Undergraduate Research

The amount of cortisol within the human body must remain at just the right level to adequately mediate the physiological stress response. With elevated cortisol levels, the immune system is suppressed, and the organism becomes vulnerable to infection. With reduced cortisol levels, the immune system is hyperactive, and the organism becomes vulnerable to autoimmune disorders. Too much or too little cortisol is lethal: clearly, cortisol levels have a great effect on human pathophysiology. The project I did provided one step in the mission to characterize the mechanism behind cortisol release. Once this is done, we will have a more thorough …


Mechanism Of Inhibition Of Influenza A Virus, Douglas Bretzing, David Busath Apr 2014

Mechanism Of Inhibition Of Influenza A Virus, Douglas Bretzing, David Busath

Journal of Undergraduate Research

The ability of influenza A virus to unpack its genome, replicate, and infect its host is contingent upon acidification of the viral interior. This is achieved by proton conductance via M2, an integral membrane protein that forms proton channels in the viral lipid envelope of influenza A virus (1). The drugs amantadine and rimantadine have previously been successful in blocking proton flux into the virus, however viral resistance to these drugs has recently reached over 90% (2). The goal of this project is to provide direct evidence as to the actual site of interaction between rimantadine and M2, thereby aiding …


Up-Regulation Of Receptors For Advanced Glycation End-Products (Rage) In The Lung Results In Significant Tissue Loss And Neonatal Lethality, Jeff Stogsdill, Dr. Paul Reynolds Apr 2014

Up-Regulation Of Receptors For Advanced Glycation End-Products (Rage) In The Lung Results In Significant Tissue Loss And Neonatal Lethality, Jeff Stogsdill, Dr. Paul Reynolds

Journal of Undergraduate Research

The receptor for advanced glycation end-products (RAGE) is becoming an increasingly popular molecule of study after having been initially characterized in relation to a number of diseases such as diabetes, Alzheimer’s and atherosclerosis among others. It has recently been noted that RAGE is found at high quantities in lung diseases such as lung fibrosis, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) coupled with emphysema, yet the specific role it plays to date is unknown. In this research, RAGE has been conditionally over-expressed in the mouse lung in order to determine its contribution to pulmonary development and …


Quantitative Assessment Of Supraorbital Osseous Bar Stability And Symmetry After Frontal Orbital Advancement For Unilateral Coronal Craniosynostosis, Aaron Hart, Chia-Chi Teng, Dr. Richard Hopper, Dr. David Khechoyan, Dr. Jennifer Brown Mar 2014

Quantitative Assessment Of Supraorbital Osseous Bar Stability And Symmetry After Frontal Orbital Advancement For Unilateral Coronal Craniosynostosis, Aaron Hart, Chia-Chi Teng, Dr. Richard Hopper, Dr. David Khechoyan, Dr. Jennifer Brown

Journal of Undergraduate Research

Abstract— Frontal-orbital advancement is the accepted surgical treatment for correcting the cranial deformity associated with premature fusion of one of the coronal cranial sutures. Removal and reshaping of the brow and lower forehead bone is performed to correct ipsilateral frontal flattening and parietal bulging, recession of the supraorbital rim, and contralateral forehead bossing. In addition to the functional aspects of the treatment, bilateral symmetry is one desirable outcome that is difficult to achieve because of the recessive movement and shape changes of the supraorbital rim that continue to occur over a prolonged period of time after the operation. Surgeons often …


Role Of Α6 Nachrs In Ethanol Modulation Of Vta Neurons, Samuel Injae Shin Mar 2014

Role Of Α6 Nachrs In Ethanol Modulation Of Vta Neurons, Samuel Injae Shin

Theses and Dissertations

The prevailing view is that enhancement of dopamine (DA) transmission in the mesolimbic system leads to the rewarding properties of alcohol and nicotine (NIC). The mesolimbic DA system consists of DA neurons in the midbrain ventral tegmental area (VTA) that innervate the nucleus accumbens (NAc). DA neurotransmission is regulated by inhibitory VTA GABA neurons, whose excitability is a net effect of glutamate (GLU) and GABA neurotransmission that are modulated by NIC cholinergic receptors (nAChRs) on afferent terminals. We have previously demonstrated that VTA GABA neurons are excited by low-dose ethanol but are inhibited by moderate to high-dose ethanol, and they …