Drug abuse; Circadian Rhythm/Chronobiology; Gene Expression; Molecular and Cellular Biology; Neuropharmacology
My laboratory seeks to understand the neurobiology of motivation and how these systems can be "highjacked" by abused substances. Substance abuse and addiction are wide-spread problems that have an enormous economic and emotional toll. Reports indicate that it costs the US upwards to $600 billion a year to deal with the health and criminal consequences and loss of productivity from substance abuse. Despite this, there are few effective treatments to combat this illness. The brain has natural systems responsible for motivating an organism to participate in behaviors that are necessary for survival, such as eating, exercise and reproduction. These same brain regions are highly sensitive to drugs of abuse, including cocaine, heroin and marijuana. My laboratory seeks to understand how these brain regions are affected by exposure to abused drugs, and in particular how the motivation to take drugs is altered by various molecular mediators in the neurons on these regions. The two basic questions we are interested in are 1) how projections from the cortex to the striatum influence drug seeking behaviors, and 2) how neurotransmitter receptors, particularly dopamine and cannbinoid receptors in these regions influence drug seeking. Our technical approaches include a number of basic behavioral models including measurements of locomotor activity, catalepsy, conditioned place preference and drug self-administration. In order to probe the circuitry of these brain regions, we use a number of advanced molecular techniques to activate and inactivate neuronal populations including optogenetics and artificial receptors. We probe the molecular pathways within the neurons by over expressing genes or knocking down expression using RNA interference. Gene delivery is accomplished using recombinant adeno-associated virus (rAAV) and several projects in the laboratory focus on improving this approach and exploring potential gene therapy applications for these vectors. The ultimate goal is to understand the basic neurobiology and molecular biology of addiction in order to develop more effective treatments for addiction.
Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular and Cellular Biology; Neurobiology; Pathophysiology; Gene Expression; Signal Transduction
Neuronal firing patterns are highly diverse because neurons regulate a wide variety of different behaviors and physiological functions including cognition and memory. Whether a neuron exhibits regular spiking, burst firing, adaptation or high frequency firing will largely be determined by which specific ion channel genes a neuron chooses to express. I am interested in a class of potassium channels that are sensitive to intracellular sodium. There are two members in this family, known as Slack and Slick, and both channel subunits are expressed in many different types of neurons. I am particularly interested in how these channels contribute to the firing patterns of pain-sensing neurons and neurons of the cerebral cortex. Understanding when, where and how these channels are working should provide important information on sensory and cortical processing and will provide insights on nociception, psychiatric disorders such as schizophrenia and bipolar disorder and neurological diseases such as epilepsy.
Reproductive Endocrinology; Apoptosis and cell death; Cell growth, differentiation and development; Endocrinology; Gene Expression; Molecular genetics; Signal Transduction; Toxicology and Xenobiotics; Vitamins and Trace Nutrient
My research focuses on developing, promoting, and evaluating effective means of pharmacology instruction at the undergraduate, graduate, professional, and interprofessional levels. Developing a competency-based curriculum in pharmacology for students at all levels, I have incorporated specific instructional methods into existing core courses that has in effect taken a sometimes intimidating subject like pharmacology and presented it to students in manageable way. Studies of the effectiveness of these methods are conducted in collaboration with the American Society of Pharmacology and Experimental Therapeutics (ASPET) and its Division of Pharmacology Education of which I am a recently appointed Fellow. Specific instructional methods in the study include: patient case presentations by dental students which utilize rubric descriptors of performance quality; Pharm Fridays with second year medical students incorporating organized lists of pertinent drugs to recognize, student-oriented learning objectives, pharmacology study guides, and active participation clicker sessions with relevant board-style pharmacology questions; development of performance-based pharmacology questions within the multidisciplinary objective structured clinical exam (OSCE) taken by all DDS candidates; and video clip presentations within classes demonstrating pertinent pharmacology topics such as medical sedation, use of emergency drugs in the clinic, and alternative means for pain management with interviews of clinical experts. These and other instructional methods in the study are highly rated by students and proven effective by outcomes on standardized exams.
Molecular and Cellular Biology; Neurobiology; Neuropharmacology
The goal of my research is the elucidation of the role of brainstem systems in motivated behaviors. My current focus is the function of neuropeptide systems, specifically urotensin II (UII). Ultimately I would like to exploit this system to better treat people with neuropsychiatric disorders. Currently my lab is pursuing the following: 1) Determine the role of UIIR activation and the UIIR expressing neurons in reward-related behaviors:. Our results support the need for further investigation of the UII-system as a therapeutic target for treating drug abuse disorders. In addition, we are investigating the i) bias-signaling properties of the endogenous UIIR ligands, and ii) the impact of UIIR single-nucleotide polymorphisms on receptor signaling. 2) Establish the contribution of cholinergic PPT to Parkinsonism-related behaviors: We designed a toxin that selectively targets UIIR expressing neurons (cholinergic PPT). In rats the toxin-mediated lesion mimics Progressive Supranuclear Palsy (the most common atypical parkinsonism) on multiple fronts: selective ablation of cholinergic PPT neurons, impaired motor function, and deficits in acoustic startle reaction (MacLaren et al, 2014a; MacLaren et al, 2014b). Similarly, the collection of deficits found after non-selective manipulations of the PPT overlap with that of Parkinson’s Disease [e.g. reduced prepulse inhibition, impaired attention, cognitive deficits, sleep disturbances]. Traditional dopamine-depletion models do not produce similar sensorimotor and cognitive deficits. Therefore, PPT lesions as an adjunct or stand alone preclinical models of Parkinsonism may be useful in identifying non-dopaminergic pharmacotherapeutics. We are pursuing further studies utilizing our selective cholinergic depletion and a viral-mediated tauopathy method with support from the CurePSP Foundation.
Addictions; Drug abuse; Behavioral pharmacology; Cytoskeleton and cell motility; Gene Expression; Gene therapy; Neurobiology; Neuropharmacology; Signal Transduction; Transcription and Translation
Drug addiction is a disabling psychiatric disease leading to enormous burdens for those afflicted, their friends and family, as well as society as a whole. Indeed, the addict will seek out and use illicit substances even in the face of severe negative financial, family and health consequences. It is believed that drugs of abuse ultimately “hijack” the reward circuitry of the CNS leading to cellular adaptations that facilitate the transition to the “addicted” state As is the case with both rodent models of drug taking, and well as throughout the global human population, not all individuals exposed to drugs of abuse will meet the classical definition of being truly “addicted”. We are looking at how molecular and behavioral plasticity mediates susceptibility to drug abuse and relapse like behaviors.
Drug abuse; Behavioral pharmacology; Signal Transduction; Neuropharmacology; Circadian Rhythm/Chronobiology
My lab‘s research seeks to understand the mechanism of action of the hormone melatonin at the MT1 and MT2 G-protein coupled receptors. We study these receptors in the brain and through the body with the goal of identifying ligands that exhibit useful binding affinity and therapeutic potential. Our team of undergraduate and graduate students, postdoctoral fellows, technicians and senior scientists work with each other and with expert co-investigators in medicinal chemistry to discover and develop novel molecules that can mimic or counteract the actions of melatonin. These molecules may help treat a variety of diseases and conditions including insomnia, circadian sleep disorders, depression, seasonal affective disorders, and cardiovascular disease. Our laboratory pursues these investigations from several angles. We assess the localization of the melatonin receptors, examine their cellular and molecular signaling mechanisms,and investigate receptor fate following prolonged exposure to melatonin. We study the distinct roles of selective MT1 and MT2 melatonin receptor ligands in modulating circadian rhythms, methamphetamine‘s ability to induce both sensitization to prolonged exposure, and stimulation of the reward system. We also study cell proliferation, survival, and neurogenesis in the brain, and the changes in gene expression underlying all these processes. Our research ultimately aims to discover novel drugs with differential actions at the MT1 and MT2 receptors. We use molecular-based drug design, computer modeling and medicinal chemistry to design and synthesize small molecules that target these receptors as agonists, inverse agonists and/or antagonists. We then pharmacologically and functionally characterize these molecules using cell-based assays and bioassays and test them in circadian and behavioral animal models.
Oncology; Cell Cycle; Cell growth, differentiation and development; Gene Expression; Molecular Basis of Disease; Molecular and Cellular Biology; Signal Transduction; Transcription and Translation
Protein phosphorylation is an essential mechanism by which intercellular signals regulate specific intracellular events. Protein kinases, the enzymes catalyzing protein phosphorylation reactions, represent a major superfamily of genes, collectively representing 2% of the protein coding potential of the human genome. Current projects in Dr. Edelman‘s lab are devoted to the role of protein kinases in prostate and ovarian cancer. These projects utilize a wide range of techniques and involve, collaboration with investigators at Roswell Park Cancer Institute to develop protein kinase-targeted therapies for both types of cancer.
Molecular and Cellular Biology; Neurodegenerative disorders; Transcription and Translation; Signal Transduction; Toxicology and Xenobiotics
My lab studies the receptor signaling mechanisms for a family of neurotrophic factors that includes ciliary neurotrophic factor (CNTF), leptin, interferon gamma, and cardiotrophin-1. These factors use the Jak/STAT pathway to regulate neuronal survival, development and response to trauma. Our interests are in how activity of the receptors and their pathway components are regulated. Currently this has focused on the impact of cellular oxidative stress on the inhibition of Jak tyrosine kinase activity. Increases in oxidative stress in neurons result in the blockade of not only CNTF family factor effects, but of many other cytokines that also use the Jak/STAT pathway for signaling such as interferons and interleukins. Non-nerve cells appear resistant to these effects of oxidative stress. Ongoing projects include testing the theory that environmental contaminants known to increase oxidative stress in cells may promote neurodegenerative diseases by inhibiting growth factor signaling. We have been studying the effects of certain heavy metals (cadmium & mercury) and pesticides (e.g. rotenone) on nerve cells in culture to determine the molecular basis for Jak inhibition. Another examines a possible role of oxidative stress in obesity. This study tests the hypothesis that the loss of the ability of the hormone leptin to regulate metabolism and appetite during obesity is a result of oxidative reactions that inhibit Jak-mediated signaling in the hypothalamus and other brain regions.
Toxicology and Xenobiotics
Dr. Paul Kostyniak‘s primary research program has focused on the toxicology of heavy metals, chlorinated organics, and antidote development. His lab is studying mechanisms of xenobiotic disposition and investigating the role of exogenous nutrients in the elimination of toxic pollutants. Other ongoing projects involve the assessment of risk associated with exposure to PCB isomers found in fresh water fish; and the development and testing of antimicrobial surface coatings. As the director of the Toxicology Research Center, Dr. Kostyniak has organized an interdisciplinary research and teaching program which applies the expertise of toxicologists, pharmacologists, chemists, acquatic biologists, biochemists, pathologists, epidemiologists, geologists and physicians to basic and applied research problems in toxicology. The Center conducts coordinated scientific inquiries into health problems created by toxic chemicals. Dr. Kostyniak also oversees the center‘s analytical toxicology laboratory and the center‘s Atlantic OSHA Professional Education Program.
Apoptosis and cell death; Endocrinology; Molecular and Cellular Biology; Gene Expression; Regulation of metabolism; Signal Transduction
Suzanne Laychock, PhD, is senior associate dean for faculty affairs and facilities, and professor of pharmacology and toxicology. She is responsible for overseeing faculty development, space management, and undergraduate biomedical education programs. Dr. Laychock earned a bachelor’s degree in biology from Brooklyn College, a master’s degree in biology for the City University of New York and a doctorate in pharmacology from the Medical College of Virginia. An accomplished scientist, Dr. Laychock’s research focuses on endocrine pharmacology with an emphasis on signal transduction mechanisms involved in insulin secretion and models of diabetes mellitus. The author of numerous journal articles, she has served as associate editor of the research journal LIPIDS, and on the editorial boards of Diabetes and the Journal of Pharmacology and Experimental Therapeutics. She is the recipient of research grants from, among others, the Juvenile Diabetes Research Foundation, the National Institutes of Health, and the American Diabetes Association. Dr. Laychock is Council Member and has chaired the Women in Pharmacology Committee of the American Society for Pharmacology and Experimental Therapeutics. She has served the university as a member and chair of the President’s Review Board, and as co-director of the Institute for Research and Education on Women and Gender.
Drug abuse; Behavioral pharmacology; Neurobiology
I have two primary research interests. First, I use pharmacological approaches to seek novel therapeutics for pain. Pain is an agonizing symptom and disease that affects millions of people. Analgesics like opioids (e.g., OxyContin) are powerful for treating many pain conditions. However, opioids are not efficacious for some pain (e.g., neuropathic pain) and prolonged use of opioids has many side effects, including tolerance and dependence. My research has found that drugs acting on imidazoline I2 receptors may produce analgesic effects that are devoid of opioid-like side effects. I am continuing this line of research to further delineate the pharmacological properties of these drugs--how they work, how effective and safe they are, and how long the beneficial effects last--as a novel class of analgesics. Second, I am interested in pharmacotherapy of stimulant abuse. Stimulants represent a large family of abused drugs, including traditional drugs of abuse such as cocaine and methamphetamine (“meth”) and valuable pharmacotherapies such as Adderall and Ritalin. Stimulant abuse and addiction remain challenging problems that lack FDA-approved pharmacotherapies. We use powerful behavioral pharmacological approaches, in animal models that are predictive of human stimulant abuse conditions, to study novel drug targets and evaluate potential pharmacotherapeutic treatments. One unifying theme of the ongoing research in my laboratory is the application of receptor theory to the guidance and interpretation of the drug interactions in behaving animals. The long-term goal of my laboratory is to develop new analgesics for pain control and pharmacotherapeutics for stimulant addiction.
Toxicology and Xenobiotics
Assessing the Health Risks of Exposures to Organophosphate (OP) Pesticides • Characterization of the in vitro and in vivo metabolism and disposition of OP pesticides in animal models and humans. • Identify new biomarkers of susceptibility to OPs by investigating the function of genetic variants in key enzymes (CYP2B6, CYP2C19, PON1) which regulate OP metabolic activation and detoxification. • Investigate the relationship between biomarkers of exposure, effect and susceptibility in human populations with environmental and occupational exposures to pesticides. • Utilize enzyme-specific physiologically based pharmacokinetic /pharmacodynamic (PBPK/PD) models to better assess human exposure, target tissue dose and subsequent effects of OPs. Assessing the Biological and Toxicological Effects of Exposures to Persistent Halogenated Aromatic Hydrocarbons, Including Dioxins, Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs). • Assessing Human Exposures to dioxins, PBDEs, and PCBs • Characterize the metabolism and disposition of dioxins, PBDEs, and PCBs in humans. • Utilize toxicogenomic approaches to understand the relationship between exposures to dioxins and/or PCBs that are ligands for the Ah receptor and mechanisms for their adverse health effects.
Ion channel kinetics and structure; Molecular and Cellular Biology; Neurobiology; Neuropharmacology
Our research program focuses on brain development, studying the development of the oligodendroglial and astroglial cell lineages in the central nervous system in normal, mutant and transgenic mice. The primary focus in the laboratory is on ion channels that regulate specification, migration and differentiation of these glial cells. The oligodendrocyte generates CNS myelin, which is essential for normal nervous system function. Thus, investigating the regulatory and signaling mechanisms that control its differentiation and the production of myelin is relevant to our understanding of brain development and of adult pathologies such as multiple sclerosis. We have recently discovered that voltage-gated Ca++ channels are necessary for normal myelination acting at multiple steps during oligodendrocyte progenitor cells (OPCs) development, however nothing is known about its role in demyelination or remyelination events. Our research aims to determine if voltage-gated Ca++ channels plays a functional role in myelin repair. Using transgenic mice and new imaging techniques we are testing the hypothesis that voltage-gated Ca++ entry promotes OPC survival and proliferation in the remyelinating adult brain. Therefore, this work is relevant to developing means to induce remyelination in myelin degenerative diseases and for myelin repair in damaged nervous tissue. Astrocytes are the most abundant cell of the human brain. They perform many functions, including biochemical support of endothelial cells that form the blood brain barrier, provision of nutrients to the nervous tissue and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries. Our lab has made the novel finding of voltage-gated Ca++ channels function in astrocyte Ca++ homeostasis, and this has implications for plasticity in astrocyte development and for Ca++ regulation in general. We are testing the hypothesis that voltage-gated Ca++ entry plays a key role in astrocyte function and glial-neuronal interactions. We have generated a conditional knockout mice for voltage-gated Ca++ channels in astrocytes, these conditional knockout mice will allow the functional analysis of voltage-gated Ca++ channels in astroglia of the postnatal and adult brain. Analyzing such mice using a combination of behavioral, electrophysiological, imaging, and immunohistochemical techniques will provide new insights in our understanding of astroglial contribution to brain function. These projects have been supported for many years by grants from the NIH and the National Multiple Sclerosis Society.
Drug abuse; Apoptosis and cell death; Molecular and Cellular Biology; Neurobiology; Signal Transduction; Toxicology and Xenobiotics
My laboratory is focused on understanding the molecular and cellular actions of drugs of abuse such as ethanol and hallucinogens such as lysergic acid diethylamide (LSD). This information is a requisite step in the ultimate development of therapeutic interventions to alleviate the major healthcare and social burden associated with use and abuse of these drugs. In addition, these drugs provide an avenue to explore the basic workings of the brain under pathological conditions that are manifested as various psychiatric disorders. Previous studies, in collaboration with Dr JC Winter in the Dept of Pharmacology and Toxicology at UB, have investigated the roles of the various serotonin receptors subtypes and their associated signaling pathways as well as glutamatergic neurotransmission in the subjective effects of LSD-type hallucinogens. Our other studies have been aimed at understanding the adverse developmental effects of ethanol exposure that result in the fetal alcohol spectrum disorders with the fetal alcohol syndrome (FAS) as the most severe manifestation. Using zebrafish and neuronal cells in culture as model systems, my laboratory in collaboration with Dr CA Dlugos in the Dept of Pathology and Anatomical Sciences at UB have investigated the morphological and histological changes associated with ethanol exposure during different developmental stages as well as the mechanisms by which developmental ethanol exposure causes neuronal loss. Currently, we are investigating the neurotoxic interaction of ethanol with pesticides. Because of the wide-spread use of pesticides, people are continually exposed both voluntarily and involuntarily to an array of toxic chemicals. In addition, since consumption of alcohol is pervasive in our society with a very high prevalence of alcohol use and abuse, it is extremely likely that people with be co-exposed to both ethanol and pesticides. Because simultaneous or sequential exposure to multiple chemicals can dramatically modify the ensuing toxicological responses, we are using both in vitro (e.g., cells in culture) and in vivo (e.g., zebrafish) model systems to begin assessing the possible health risk of co-exposure to ethanol and pesticides. Using the herbicide paraquat, which is widely used throughout the world, as a test compound, we have found that ethanol synergistically increases the in vitro neurotoxicity of this pesticide. Our efforts are now aimed at ascertaining whether a similar interaction occurs in vivo as well as determining the molecular mechanism responsible for this synergistic neurotoxicity. Teaching is a naturally complement to research. Accordingly, I have also been engaged in efforts to both improve how we provide the knowledge base to our undergraduate, graduate, and professional students, and also how we help students learn to integrate and apply this information in problem-solving at the clinical and basic science levels. Efforts include: 1. using “clickers” in large class formats to assess student’s understanding of the material and well as provide each student instantaneous feedback for their own self-assessment; 2. using cases studies and a small group learning format; and 3. Having students write short grant proposals based upon the current literature as well as reviewing and critiquing their classmate’s proposals.
Bioinformatics; Genomics and proteomics; Signal Transduction; Toxicology and Xenobiotics
Our laboratory seeks to understand hormone-triggered nuclear receptor signaling. Nuclear receptors are associated with various diseases including diabetes and cancer and the availability of several high resolution structures of their ligand binding domains make them attractive targets for drug discovery. Eight of the top 100 prescription drugs (accounting for about US $9 billion in sales) target a nuclear receptor. However, these drugs can cause a variety of side effects and some patients develop drug resistance. Tamoxifen, a drug designed to selectively target the nuclear estrogen receptor which is present in 70% of breast cancer patients, induces substantial regression of breast tumors and an increase in disease-free survival. Tamoxifen binds directly to the ligand binding domain of estrogen receptor and regulates estrogen-mediated growth of breast cancer cells. Tamoxifen mimics estrogen effects in other tissues thereby providing some beneficial effects including reduced risk of osteoporosis. However, breast cancers that initially respond well to tamoxifen tend to develop resistance and resume growth despite the continued presence of the antagonist. We specifically focus on protein interactions that regulate estrogen signaling by binding to estrogen receptors. Our objective is to identify the estrogen receptor conformation-sensing regions of the interacting proteins and to discover potential small molecule sensors using state-of-the art bioinformatics and structure-based discovery tools and use them to generate a new breed of small molecular therapeutics for breast cancer therapy.
Neurodegenerative disorders; Apoptosis and cell death; Membrane Transport (Ion Transport); Proteins and metalloenzymes; Signal Transduction; Toxicology and Xenobiotics
Dr. Jerome Roth‘s research interests over the past several years have focused on the mechanism of action of manganese in producing neuronal cell death. Manganese is an essential mineral that at high concentration acts as a neurotoxin which produces a Parkinson-like syndrome. Although the identified brain lesions associated with manganism differ from those of Parkinson’s disease, there is increasing evidence that chronic exposure to Mn correlates with increased susceptibility to develop Parkinsonism. Current studies are focused on characterizing the signal transduction pathways stimulated by manganese and to determine whether they also play a role in the toxic actions of this divalent cation. As part of this project we are also investigating the transport mechanisms by which manganese is taken up into cells. We have focused our studies on the divalent metal transporter (DMT1) and its role in the transport of manganese and other divalent cations. We are currently studying the transcriptional and post-translational factors that regulate its expression in vivo. Preliminary studies have linked DMT1 expression to the protein, parkin, mutations in which lead to early onset of Parkinson‘s disease. Whether other gene linked to Parkinsonism are also associate with development of manganism is the current focus of my research. Current studies in my laboratory focus on how other early and late genes associated with Parkinson’s disease can influence Mn toxicity as these studies will provide a basis for the comorbidity between manganism and Parkinson’s; the manipulation of this mechanism may therefore provide new prophylactic and/or management treatment options for Parkinson’s disease.
Genomics and proteomics; Molecular and Cellular Biology; Regulation of metabolism; Toxicology and Xenobiotics
Dr. David Shubert has been at the University at Buffalo since 2006. He received is B.S in Pharmacy from Duquesne University and a Ph.D from the University at Buffalo. His research interests include the mechanism by which environmental chemicals initiate and promote cancer. He is the Assistant Dean for Biomedical Undergraduate Education and teaches pharmacology, toxicology and cardiovascular physiology. Dr. Shubert accepts undergraduate students interested in pursuing research in his areas of interest. He is an active member of the Society of Toxciology.
Genomics and proteomics; Neurobiology; Neurodegenerative disorders
My lab investigates the molecular control of cell fate and homeostasis of resident stem and progenitor cells in the human brain. Using a combination of multicolor cell sorting techniques and whole genome analysis, we are characterizing the signaling pathways which regulate the formation and fate of human oligodendrocyte progenitor cells. We are testing the functional significance of these pathways using both pharmacological and viral methods in culture and animal-based models of myelination and demyelination.
Behavioral pharmacology; Cardiac pharmacology; Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular Basis of Disease; Neurobiology; Neuropharmacology; Signal Transduction; Transgenic organisms
With over 400 genes coding for them in humans, ion channels play a significant role in most physiological functions. Drug-induced channel dysfunction often leads to a variety of disorders and results in significant incidence of serious injury and death. We investigate molecular mechanisms underlying neurodegenerative disorders and cardiac arrhythmias induced by ion channel dysfunction arising from genetic factors and/or drug interactions. The tools used for these investigations include genetic, electrophysiologic, pharmacologic, molecular and cell culturing methods. Preparations used for experiments include Drosophila as a genetic model system, and human cell lines expressing human ion channels that play an important role in critical-to-life functions including cardiac rhythm, respiration and the central nervous system.
Behavioral pharmacology; Neuropharmacology; Toxicology and Xenobiotics
Research in my laboratory centers on the study of psychoactive drugs with special emphasis on nootropics and drugs of abuse. In collaboration with Dr. Richard Rabin of this department, behavioral data are correlated with biochemical indices of drug action in an attempt to understand at the receptor level the effects in intact animals of psychoactive drugs. Behavioral data are obtained using the techniques of operant behavior with special emphasis on the phenomenon of drug-induced stimulus control. Current interests include the serotonergic basis for the actions of indoleamine and phenethylamine hallucinogens including LSD and [-]-DOM as well as their interactions with selective monoamine reuptake inhibitors such as fluoxetine [Prozac]. In the area of nootropics, recent studies have examined the effects of EGb 761, an extract of Ginkgo biloba; for these investigations, a delayed non-matching to position task in a radial maze is employed. Currently, studies are in progress to assess the serotonergic basis for the cognitive effects of drugs of abuse including LSD and MDMA [Ecstasy]. Behavioral pharmacology of psychoactive drugs, including psychotherapeutic agents and drugs of abuse; mechanisms of action of hallucinogens. Research in Dr. Jerrold Winter‘s laboratory seeks to understand the ways in which drugs alter behavior. Many chemicals are candidates for study but attention in the last few years has centered on hallucinogens such as LSD, phencyclidine, DOM, and ibogaine. Another area of major interest is age-related memory impairment and those natural materials, including ginseng and gingko biloba, which are purported to influence that impairment. The behavioral effects of these drugs are studied in rats trained with the techniques of operant conditioning. Specific variables in use at the present time include drug-induced stimulus control, radial maze acquisition and performance, and conditioned place preference and aversion. In addition, Dr. Winter actively collaborates with Dr. Richard Rabin of the Department of Pharmacology and Toxicology in order to correlate behavioral effects with biochemical indices of action at the receptor level and with functional efficacies in second messenger systems.