Effects of sub-chronic methylphenidate on risk-taking and sociability in zebrafish (Danio rerio).

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2020-08

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Abstract

Attention deficit hyperactive disorder (ADHD) is the most common psychiatric disorder in children affecting around 11% of children 4-17 years of age (CDC 2019). Children with ADHD are widely treated with stimulant medications such as methylphenidate (Ritalin®). However, there has been little research on the developmental effects of methylphenidate on risk-taking and sociability. We investigated in zebrafish the potential developmental neurobehavioral toxicity of methylphenidate on these behavioral functions. We chose zebrafish because they provide a model with extensive genetic tools for future mechanistic studies. We studied whether sub-chronic methylphenidate exposure during juvenile development causes neurobehavioral impairments in zebrafish. Methylphenidate diminished responses to environmental stimuli after both acute and sub-chronic dosing. In adult zebrafish, acute methylphenidate impaired avoidance of an approaching visual stimulus modeling a predator and decreased locomotor response to the social visual stimulus of conspecifics. Adult zebrafish dosed acutely with methylphenidate demonstrated behaviors of less retreat from threatening visual stimuli and less approach to conspecifics compared with controls. In a sub-chronic dosing paradigm during development, methylphenidate caused less robust exploration of a novel tank. In the predator avoidance paradigm, sub-chronic dosing that began at an older age (28 dpf) decreased activity levels more than sub-chronic dosing that began at earlier ages (14 dpf and 21 dpf). In the social shoaling task, sub-chronic methylphenidate attenuated reaction to the social stimulus. Acute and developmental methylphenidate exposure decreased response to environmental cues. Additional research is needed to determine critical mechanisms for these effects and to see how these results may be translatable to neurobehavioral toxicity of prescribing Ritalin® to children and adolescents.

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10.1007/s00210-020-01835-z

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Brenner, Rebecca G, Anthony N Oliveri, Walter Sinnott-Armstrong and Edward D Levin (2020). Effects of sub-chronic methylphenidate on risk-taking and sociability in zebrafish (Danio rerio). Naunyn-Schmiedeberg's archives of pharmacology, 393(8). pp. 1373–1381. 10.1007/s00210-020-01835-z Retrieved from https://hdl.handle.net/10161/29501.

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Scholars@Duke

Sinnott-Armstrong

Walter Sinnott-Armstrong

Chauncey Stillman Distinguished Professor of Practical Ethics

Walter Sinnott-Armstrong is Chauncey Stillman Professor of Practical Ethics in the Department of Philosophy and the Kenan Institute for Ethics at Duke University. He has secondary appointments in the Law School and the Department of Psychology and Neuroscience, and he is core faculty in the Duke Center for Cognitive Neuroscience, the Duke Institute for Brain Sciences, and the Duke Center for Interdisciplinary Decision Sciences. He serves as Resource Faculty in the Philosophy Department of the University of North Carolina at Chapel Hill, Partner Investigator at the Oxford Centre for Neuroethics, and Research Scientist with The Mind Research Network in New Mexico. He has visited at National Cheng Kung University in Taiwan, the Macquarie Research Center for Agency, Values, and Ethics in Australia, and the National Institutes of Health in Washington. He has received fellowships from the Harvard Program in Ethics and the Professions, the Princeton Center for Human Values, the Oxford Uehiro Centre for Practical Ethics, the Center for Applied Philosophy and Public Ethics at the Australian National University, and the Sage Center for the Study of the Mind at the University of California, Santa Barbara. He has served as co-chair of the Board of Officers of the American Philosophical Association, co-director of the MacArthur Law and Neuroscience Project, and co-PI of the project on the Neuroscience and Philosophy of Free Will and Moral Responsibility at Chapman University. He earned his bachelor’s degree from Amherst College and his doctorate from Yale University. He has published widely on ethics (theoretical and applied as well as meta-ethics), empirical moral psychology and neuroscience, philosophy of law, epistemology, philosophy of religion, and informal logic. Most recently, he is the author of  Think Again: How to Reason and Argue, Morality Without God?and Moral Skepticisms; co-author with Robert Fogelin of Understanding Arguments, Ninth Edition, and with Jesse Summers of Clean Hands: Philosophical Lessons of Scrupulosity; and editor of Moral Psychology, volumes I-V. His numerous articles have appeared in a variety of philosophical, scientific, and popular journals and collections. He performs various experiments in moral psychology and brain science with his Moral Attitudes and Decisions (MAD) Lab. He is working on one book on moral artificial intelligence and another book that will develop a contrastivist view of freedom and responsibility. He co-directs Summer Seminars in Neuroscience and Philosophy (SSNaP) with Felipe De Brigard and teaches a popular MOOC, Think Again, on the Coursera website with Ram Neta. 

Levin

Edward Daniel Levin

Professor in Psychiatry and Behavioral Sciences

Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. His primary academic appointment is as Professor in the Department of Psychiatry and Behavioral Sciences. He also has secondary appointments in the Department Pharmacology and Cancer Biology, the Department of Psychological and Brain Sciences and the Nicholas School of the Environment at Duke. His primary research effort is to understand basic neural interactions underlying cognitive function and addiction and to apply this knowledge to better understand cognitive dysfunction and addiction disorders and to develop novel therapeutic treatments.

The three main research components of his laboratory are focused on the themes of the basic neurobiology of cognition and addiction, neurobehavioral toxicology and the development of novel therapeutic treatments for cognitive dysfunction and substance abuse. Currently, our principal research focus concerns nicotine. We have documented the basic effects of nicotine on learning memory and attention as well as nicotine self-administration. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance not only in normal rats, but also in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on alpha7 and alpha4beta2 nicotinic receptor subtypes in the hippocampus, amygdala , thalamus and frontal cortex and how they interact with dopamine D1 and D2 and glutamate NMDA systems with regard to memory and addiction. I am also conducting studies on human cognitive behavior. We have current studies to assess nicotine effects on attention, memory and mental processing speed in schizophrenia, Alzheimer's Disease and Attention Deficit Hyperactivity Disorder. In the area of neurobehavioral toxicology, I have continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary project in neurobehavioral toxicology focuses on the cognitive deficits caused by the marine toxins. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation.


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