Neurotoxicology of nicotine and tobacco

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2022-01-01

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Abstract

Nicotine exposure causes well characterized neurotoxic effects, which are highly dependent on the age of exposure. During early development, nicotine exposure causes persistent neural and behavioral impairments, even with low doses modeling second-hand or environmental tobacco smoke exposure. Nicotine-induced neurodevelopmental toxicity is seen across a variety of neural systems and behavioral functions in a spectrum of species from sea urchins, fish and birds to mice and rats to monkeys and humans. In addition to early development, adolescence is also a vulnerable period for nicotine neurotoxicity with persisting effects on nicotinic receptor regulation and increased liability to nicotine self-administration. Fewer neurotoxic signs of moderate doses of nicotine are seen in adults and during aging. In fact, there is some evidence for potential therapeutic effects of nicotine and similar chemicals for particularly for treating cognitive impairment. The principal neurotoxic effects of moderate nicotine doses in adults derive from the fact that nicotine is the main driving force underlying tobacco addiction resulting in the self-administration of a variety of neurotoxic chemicals. Future research concerning nicotine neurotoxicity should include the interactions of nicotine effects with other toxic chemicals in tobacco, in e-cigarettes, in co-administered drugs of abuse and environmental toxicants.

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10.1016/bs.ant.2022.06.003

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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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