Critical developmental periods for effects of low-level tobacco smoke exposure on behavioral performance.
Abstract
Tobacco exposure during development leads to neurobehavioral dysfunction in children, even when exposure is limited to secondhand smoke. We have previously shown in rats that developmental exposure to tobacco smoke extract (TSE), at levels mimicking secondhand smoke, starting preconception and extending throughout gestation, evoked subsequent locomotor hyperactivity and cognitive impairment. These effects were greater than those caused by equivalent exposures to nicotine alone, implying that other agents in tobacco smoke contributed to the adverse behavioral effects. In the present study, we examined the critical developmental windows of vulnerability for these effects, restricting TSE administration (0.2 mg/kg/day nicotine equivalent, or DMSO vehicle, delivered by subcutaneously-implanted pumps) to three distinct 10 day periods: the 10 days preceding mating, the first 10 days of gestation (early gestation), or the second 10 days of gestation (late gestation). The principal behavioral effects revealed a critical developmental window of vulnerability, as well as sex selectivity. Late gestational TSE exposure significantly increased errors in the initial training on the radial-arm maze in female offspring, whereas no effects were seen in males exposed during late gestation, or with either sex in the other exposure windows. In attentional testing with the visual signal detection test, male offspring exposed to TSE during early or late gestation showed hypervigilance during low-motivating conditions. These results demonstrate that gestational TSE exposure causes persistent behavioral effects that are dependent on the developmental window in which exposure occurs. The fact that effects were seen at TSE levels modeling secondhand smoke, emphasizes the need for decreasing involuntary tobacco smoke exposure, particularly during pregnancy.
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Cauley, Marty, Brandon J Hall, Yael Abreu-Villaça, Shaqif Junaid, Hannah White, Abtin Kiany, Theodore A Slotkin, Edward D Levin, et al. (2018). Critical developmental periods for effects of low-level tobacco smoke exposure on behavioral performance. Neurotoxicology, 68. pp. 81–87. 10.1016/j.neuro.2018.07.012 Retrieved from https://hdl.handle.net/10161/29581.
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![Slotkin](https://scholars.duke.edu/profile-images/thumbnail200/0097983.jpg)
Theodore Alan Slotkin
We study the interaction of drugs, hormones and environmental factors with the developing organism, with particular emphasis on the fetal and neonatal nervous system. The role of biochemical factors mediating development of nerve cells and other types of tissue is a major thrust, since they influence the subsequent structural and physiological status of critical organ systems. Ongoing projects comprise five areas: (1) Mechanisms regulating development of synapses - role of endocrine and other trophic factors, intracellular messengers in developing cells, control of target organ differentiation by neural input; (2) Adverse effects of exogenous agents on development, with an emphasis on identification of mechanisms by which behavioral or physiological damage occurs - drugs of abuse (especially nicotine), hormonal imbalances, environmental contaminants (especially pesticides), food additives, intrauterine growth retardation, fetal and neonatal hypoxia; (3) Control of fetal and neonatal cardiovascular and respiratory function by the immature nervous system - normal physiological mechanisms, responses to stress, factors mediating the transition from fetal to neonatal function, reactivity during delivery, Sudden Infant Death Syndrome; (4) Breast cancer cell growth regulation - role of hormone and neurotransmitter receptors converging on common cell signaling mechanisms, and targeting of these receptors for cancer therapeutics.
![Levin](https://scholars.duke.edu/profile-images/thumbnail200/0099352.jpg)
Edward Daniel Levin
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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