David Shurtleff - Academia.edu (original) (raw)

Papers by David Shurtleff

Neuropharmacology, 2014

In 1974, the United States Congress established the National Institute on Drug Abuse (NIDA) as th... more In 1974, the United States Congress established the National Institute on Drug Abuse (NIDA) as the responsible Federal agency for conducting basic, clinical, and epidemiological research to improve the understanding, prevention, and treatment of drug abuse and addiction and their health consequences. Throughout its 40 year history, NIDA's mission has been to bring the power of science to bear on the problem of drug abuse and addiction. NIDA's intramural research program (now in Baltimore MD) grew out of the Addiction Research Center in Lexington, KY, and, at the time of its establishment, NIDA assumed control of the Drug Abuse Warning Network and the National Household Survey on Drug Abuse. Early on, NIDA-supported research focused on opiate addiction and its treatment, which led to the discovery of the opiate receptors and their binding sites. NIDA-supported research continues at a rapid pace and some of the more recent and exciting opiate research is highlighted in three articles in this special issue. Pasternak's (2014) article reveals the complexity of the mu opioid receptor gene and its many splice variants, which may provide drug targets for new opiate analgesics without abuse liability or risk of respiratory depression. Charbogne et al. (2014) champion the use of mutant mice in exploring the role of the mu, delta and kappa receptors in drug abuse, and the viability of the receptors as targets for medications development. Hutchinson and Watkins (2014) review the unique role of opioid activation of central immune signaling and they present groundbreaking evidence that drug-induced activation of central immune mechanisms can increase activation of mesolimbic dopamine reward pathways. Moving beyond opioids, Piomelli (2014) reviews what we know about lipid-derived signaling molecules that activate cannabinoid receptors (i.e., endocannabinoids) and their involvement in stress, pain, emotion, motivation and energy balance. He describes what is known about the molecules themselves, receptors, and enzyme-mediated cleavage, and what is needed to understand their role in drug abuse and addiction. Volkow and Baler (2014) give an excellent summary of many of the advances that NIDA-sponsored research has produced, from the development of brain imaging technology to new tools that can identify genes, epigenetic marks, and neuronal circuits (e.g., optogenetics and designer drug receptors). These advances have stimulated unprecedented growth in our understanding of drug abuse and addiction. The review by Parker et al. (2014) discusses recent advances that are making it possible to fine-map quantitative trait loci (QTLs) and to study "knocked-out" genes in rats, which will improve the ability of addiction scientists to study the genetic basis of addiction using robust animal models. Research reviewed by several eminent investigators in this special issue describes in exquisite detail the functional role of

Journal of Experimental Psychology: Animal Behavior Processes, 1985

Experimental and Clinical Psychopharmacology, 2000

This commentary examines and reinterprets the concept of relative persistence in drug self-admini... more This commentary examines and reinterprets the concept of relative persistence in drug self-administration studies, described by R. A. Meisch (2000), in behavioral economic terms. Over the past several years, investigators in the behavioral sciences have successfully applied consumer demand theory to the study of drug abuse and addiction. The economic concept of demand elasticity (i.e., the changes in the amount of a commodity demanded as a function of changes in price) and the concept of unit price are described in detail, and this commentary shows these concepts provide an alternative interpretation to the relative persistence of behavior. The application of the behavioral economic approach to understanding abuse potential of putative drugs of abuse, in development of medications for drug addiction and in characterizing the transition from drug use to drug addiction, is discussed.

Drug and Alcohol Dependence, 2007

Research on the neural basis of drug addiction has established that the neurobiological substrate... more Research on the neural basis of drug addiction has established that the neurobiological substrates that subserve motivated behavior, reward processes, and learning and memory also underlie compulsive drug use (Hyman et al., 2006). At the cellular and molecular levels of analyses, there are biophysical, genetic and epigenetic, neuro-pharmacological, intracellular, and morphological changes that occur in particular brain regions after drug exposure. Because drug seeking and other behaviors associated with addiction may be a direct result of altered genetic and cellular networks (Freeman and Vrana, 2006), neuroscientists are exploring the involvement of a wide array of brain circuits and neuroplastic changes associated with drug abuse to drug addiction. Intracranial selfadministration studies, for example, have identified regions of the mesocorticolimbic dopamine system as playing a key role in the rewarding properties of drugs of abuse, and this system has been identified as the major neural substrate for the reinforcing effects of opiates, psychostimulants, ethanol, nicotine, and marijuana. Research has further shown that specific brain regions, such as the bed nucleus of the stria terminalis, ventral tegmental area, nucleus accumbens, amygdala, hippocampus and frontal cortex, are involved in various aspects of the drug addiction process.

Drug and Alcohol Dependence, 2008

Together with a previously released request for applications (RFA DA06-004), the symposium repres... more Together with a previously released request for applications (RFA DA06-004), the symposium represented NIDA's interest in understanding the neurobiological mechanisms underlying the social psychological antecedents and consequences of drug abuse and addiction. This article briefly presents the rationale for that interest, summarizes the presentations at the symposium, and presents research priorities for NIDA and those identified by the participants. The social environment is multifaceted and comprises a dynamic set of environmental and behavioral interactions that influence the connections among individuals such as parent and child, husband and wife, groups, institutions, and societies. These connections,

The Journal of Neuroscience, 2019

The Journal of Neuroscience, 2018

Background on the National Institutes of Health BRAIN Initiative and neuroethics The National Ins... more Background on the National Institutes of Health BRAIN Initiative and neuroethics The National Institutes of Health (NIH) works tirelessly to support the best science and ensure that its funded research adheres to the highest ethical standards. From its inception, the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, an ambitious effort focused on understanding the human brain, has made a concerted effort to integrate neuroethics into its science, motivated by the understanding that brain circuit activity is the foundation of individual human experiences and is uniquely entwined with our sense of personal identity. In the 5 years since the Initiative began, NIH has invested over $950 million in BRAIN Initiative research throughout the United States and around the world to develop novel tools and neurotechnologies that will enable unprecedented detailed maps of neural circuits, measures of the fluctuating patterns of electrical and chemical activity flowing within those circuits, and understanding of how their interplay creates our cognitive and behavioral capabilities. Understanding neural circuit function is essential if we are to transform our ability to diagnose and treat neurological, mental health, and substance use disorders, which are the leading cause of disability in the United States. For this diverse group of disorders, the burden of illness results

The Lancet, 2009

Cigarette smoking is a leading cause of death in the USA. The practice has been linked to 440 000... more Cigarette smoking is a leading cause of death in the USA. The practice has been linked to 440 000 preventable deaths per year, mainly due to lung cancer (123 836), coronary heart disease (86 801), and respiratory disease and chronic obstructive pulmonary disease (90 582). 1,2 These deaths are the outcome of nicotine addiction, which compels individuals to use tobacco despite the known adverse health consequences. Sadly, priorities for investment in clinical trials are directed at treatment of diseases caused by continued tobacco use, rather than addressing the root cause of the diseases: nicotine addiction (figure). Moreover, clinical trials for smoking cessation and treatment of nicotine addiction are not even within the top 25 therapeutic categories in development by the drug industry; anticancer treatments are the first priority. 3 174 pharmacotherapy trials were done for smoking cessation (46 supported by industry) com pared with 1490 for lung cancer (544 supported by industry).

Journal of the Experimental Analysis of Behavior, 1987

Journal of the Experimental Analysis of Behavior, 1990

Bulletin of the Psychonomic Society, 1979

Physical therapy, 2017

One in five Americans experiences disability that affects their daily function because of impairm... more One in five Americans experiences disability that affects their daily function because of impairments in mobility, cognitive function, sensory impairment, or communication impairment. The need for rehabilitation strategies to optimize function and reduce disability is a clear priority for research to address this public health challenge. The National Institutes of Health (NIH) recently published a Research Plan on Rehabilitation that provides a set of priorities to guide the field over the next 5 years. The plan was developed with input from multiple Institutes and Centers within the NIH, the National Advisory Board for Medical Rehabilitation Research, and the public. This article provides an overview of the need for this research plan, an outline of its development, and a listing of six priority areas for research. The NIH is committed to working with all stakeholder communities engaged in rehabilitation research to track progress made on these priorities and to work to advance the...

Seminars in cell & developmental biology, 2009

Zeitschrift für Psychologie, 2014

Recent findings from placebo research corroborate the evidence that the placebo effect represents... more Recent findings from placebo research corroborate the evidence that the placebo effect represents a promising model to shed new light on brain-mind-body interactions. In particular, this research has partially elucidated the role of how patients’ expectations and the quality of physician-patient communication can influence the efficacy of interventions and overall clinical outcomes. Accordingly, the study of the placebo effect should be incorporated in the core clinical practice curriculum of all health practitioners. While the growing knowledge about the placebo effect points to it being an irreducible primary reality of medical practice, an ethical analysis aimed at avoiding the misuse of placebos and maximizing beneficial placebo effects is needed.

The Scientific World JOURNAL, 2007

Journal of Neuroimmune Pharmacology, 2012

Researchers have recently demonstrated the presence of anti-HIV-1 microRNAs (miR-28, miR-125b, mi... more Researchers have recently demonstrated the presence of anti-HIV-1 microRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) in monocytes, macrophages, and CD4+ T cells, which are the primary targets of HIV infection. These miRNAs appear to regulate the level of infectivity of HIV-1 in the target cells, and thus have an impact on HIV-1 latency. The levels of these miRNAs are significantly higher in resting CD4+ T cells than those in active CD4+ T cells, whereas HIV-1 infectivity is greater in active than in resting CD4+ T cells. Similarly, the levels of these miRNAs are significantly higher in monocytes than in macrophages, whereas HIV-1 infectivity is greater in macrophages than in monocytes. Down-regulation or inhibition of the activity of these miRNAs can promote replication of latent HIV-1 in resting CD4+ T cells and in monocytes. Recently, morphine was shown to down regulate the expression of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in cultured human monocytes and this effect of morphine was mediated via activation of mu opioid receptors (MOR). In addition, levels of these anti-HIV miRNAs were significantly lower in the peripheral blood mononuclear cells (PBMCs) isolated from heroin-dependent subjects than those from control subjects. These findings raise an important question: Does morphine have potential to activate latent HIV-1 in resting CD4+ T cells and macrophages, including microglia of human subjects maintained on highly active antiretroviral therapy (HAART)? Further research is required to answer this question.

Physiology & Behavior, 2008

On May 31–June 2, 2006 the National Institute on Drug Abuse (NIDA) sponsored a scientific worksho... more On May 31–June 2, 2006 the National Institute on Drug Abuse (NIDA) sponsored a scientific workshop entitled, “Obesity and Addiction: Common Neurological Mechanisms and Drug Development.” This workshop represented NIDA's interest in understanding the neurobiological mechanisms and neuronal systems underlying obesity and drug addiction and in identifying potential molecular targets for treatment interventions. Several of the papers from the conference have been published in two recent volumes of Physiology and Behavior (see citations below). This report serves to highlight some of the findings presented at themeeting and to provide a state of the science update for drug addiction and obesity researchers. Compulsive eating, leading to obesity, and compulsive drug use, leading to addiction, are major health problems in the United States. Together, these disorders of appetitive motivation account for approximately one million deaths per year. Although many of the mechanisms of compulsive eating and compulsive drug use remain to be discovered, there is evidence for considerable convergence of the neurophysiological substrates of food and drug reward. Addictive drugs do indeed appear to “hijack” neural mechanisms of natural reward to some extent. Recent national surveys confirm that obesity in the U.S. is on the rise, particularly among school age children. Obesity is associated with elevated incidence of heart disease, stroke, high blood pressure, and cancer, and is recognized by government agencies (e.g., CDC) as among the most pressing public health issues today. In order to prevent and treat obesity, it is imperative that we understand the biological mechanisms underlying its development. NIDA supported research has shown that the activity of dopamine neurons and reduced dopamine D2 receptor availability in the ventral striatum have been associated with obesity and drug addiction. It has been hypothesized, therefore, that a reduction in the level of D2 receptors may increase the reinforcing value of drugs of abuse as well as of natural reinforcers, such as food. Indeed, dopamine mechanisms and associated neurocircuitry may be one of several important neurobiological factors linked to a range of compulsive behaviors including compulsive drug and food intake. The papers presented at the NIDA Obesity and Addiction conference focused on research examining mechanisms beyond the

Physiology & Behavior, 1988

The hypothesis that DFP alters circadian rhythms by altering the output of an "internal ... more The hypothesis that DFP alters circadian rhythms by altering the output of an "internal clock" which is also used to time events in behavioral tasks was tested. Since any clock has a mean rate (ticks/unit time) and an associated variance (changes in the rate across time), measures of time perception which depend upon both the mean clock rate and its variance (discriminability, A'), or only the mean clock rate (Bisection Point) were examined. In Experiment 1, two groups of rats were trained to discriminate between a standard duration and six comparison durations of a light. Six weeks following three injections of DFP (1.0 mg/kg/week) or vehicle (saline and 5% alcohol), the discriminability (A') between the standard and comparison durations was reliably reduced for the DFP-treated animals. In Experiment 2, rats were trained to perform on a temporal bisection task. Relative to performance during the weeks following vehicle (peanut oil) treatments, discriminability (A') during the weeks following treatment with DFP (1.0 mg/kg/week) was reliably degraded but measures of the Bisection Point were unaffected. Since Experiments 1 and 2 both used a light duration as a discriminative stimulus, Experiment 3 examined the possibility that DFP treatments produced a change in visual function rather than clock function. Two groups of rats were trained to discriminate between light-on and light-off periods in a standard free-operant successive discrimination paradigm. No changes in discriminability or response rates were evident following two injections of DFP (1.0 mg/kg/week) or vehicle (peanut oil).(ABSTRACT TRUNCATED AT 250 WORDS)