Neurotoxicity of Drugs of Abuse

Dr. Lucio G. Costa is Professor of Toxicology at the University of Washington in Seattle, and of Pharmacology/Toxicology at the University of Parma Medical School. He received a doctorate in Pharmacology from the University of Milano in 1977, and was a postdoctoral fellow at the University of Texas at Houston. He is a member of several national and international professional organizations, a Fellow of the Academy of Toxicological Sciences, and a European Certified Toxicologist. He received various award for his scientific accomplishments, including the Achievement Award from the Society of Toxicology. He serves in various editorial capacities for several toxicology journals, and is an active manuscript and grant reviewer. Dr. Costa has been the member of dozens of panels and committees at the national and international level dealing with toxicology and risk assessment issues. He has chaired and/or organized symposia at scientific meetings in the United States and internationally. He has been teaching classes in the area of toxicology, neurotoxicology and pharmacology to graduate and medical students for 30 years. He keeps an active research program in the area of neurotoxicology. Dr. Aschner serves as the Harold and Muriel Block Chair in Molecular Pharmacology at Albert Einstein College of Medicine. He served on numerous toxicology panels (Institute of Medicine, US Environmental Protection Agency, Center for Disease Control), and is a member of the Neurotoxicology and Alcohol study section (NIH). Research in our lab focuses on the following topics: (1) Modulation of C. elegans genes (aat, skn-1, daf-16) that are homologous to mammalian regulators of MeHg uptake and cellular resistance will modify dopaminergic neurodegeneration in response to MeHg exposure. (2) Under conditions of MeHg-induced oxidative stress, Nrf2 (a master regulator of antioxidant responses) coordinates the upregulation of cytoprotective genes that combat MeHg-induced oxidative injury, and that genetic and biochemical changes that negatively impact upon Nrf2 function increase MeHg’s neurotoxicity. (3) PARK2, a strong PD genetic risk factor, alters neuronal vulnerability to modifiers of cellular Mn status, particularly at the level of mitochondrial dysfunction and oxidative stress. Our studies are designed to (1) shed novel mechanistic insight into metal-induced neurodegeneration; (2) identify targets for genetic or pharmacologic modulation of neurodegenerative disorders; (3) increase knowledge of the pathway involved in oxidative stress; (4) develop improved research models for human disease using knowledge of environmental sciences. Dr. William Slikker, Jr. was the director of FDA’s National Center for Toxicological Research (NCTR) before his retirement. He received his Ph.D. in pharmacology and toxicology from the University of California at Davis. Dr. Slikker holds adjunct professorships in the Department of Pediatrics, as well as the Department of Pharmacology and Toxicology at the University of Arkansas for Medical Sciences. He has held committee chairmanships or elected offices in several scientific societies including the Teratology Society (serving as president) and the American Society for Pharmacology and Experimental Therapeutics (chair, Developmental Pharmacology Section and member, Program Committee). Dr. Slikker is also the co-founder and past president of the MidSouth Computational Biology and Bioinformatics Society. He is currently associate editor for NeuroToxicology and associate editor for the “Environmental Health” section of Experimental Biology and Medicine. He is the past president of The Academy of Toxicological Sciences and the Society of Toxicology. He is a recipient of the 2014 George H. Scott Memorial Award from The Toxicology Forum and was invited to present the Warkany Lecture at the 2015 annual meeting of the Teratology Society. In early 2019, the Academy of Toxicological Sciences selected Dr. Slikker to receive the prestigious Mildred S. Christian Career Achievement Award. The Society for Birth Defects Research and Prevention selected Dr. Slikker to be the recipient of the 2022 Edward W. Carney Distinguished Service Award. Dr. Slikker has authored or co-authored over 380 publications in the areas of transplancentalpharmacokinetics, developmental neurotoxicology, neuroprotection, systems biology, and risk assessment. Dr. Slikker’s recent research has highlighted the concern for thousands of infants and toddlers who undergo longer-duration general anesthesia. He has performed research with his team and published over 25 peer-reviewed papers outlining the issue of brain-cell death and cognitive-function deficits in animal models that may result from several hours of anesthesia at a critical time of development. He has also, with the use of in vitro and in vivo techniques in rodents and nonhuman primates, defined possible mechanisms of toxicity and protective pathways to prevent the detrimental effects of general anesthesia. Through these and related scientific contributions, he has identified and characterized a host of minimally invasive biomarkers of neurotoxicity including the use of preclinical imaging (MRI, MicroPET/CT), genomic and lipidomic analysis, and modeling approaches to characterize and quantify adult and developmental neurotoxicity. He has also served on several national/international advisory panels for ILSI, HESI, CIIT, EPA, NIEHS, NAS, NIH and WHO.

Preface William Slikker, Jr. 1. Cannabinoids G. Jean Harry 2. Converging mechanisms in ethanol neurotoxicity Miriam Beatriz Virgolini and Ricardo Marcos Pautassi 3. Neurotoxicology of nicotine and tobacco Edward D. Levin 4. The neurotoxic potential of opioids including fentanyl and fentanyl analogs R. Daniel Mellon 5. Phencyclidine (PCP)-induced neurotoxicity and behavioral deficits Cheng Wang, Shuliang Liu, Leah E. Latham, Fang Liu, Tucker A. Patterson and William Slikker Jr 6. The mysterious beauty of ketamine: benefits and risks Donald R. Mattison, Abdallah Alami, Thomas J. Moore and G. Caleb Alexander