Attention and working memory deficits in a perinatal nicotine exposure mouse model.

Lin Zhang,Thomas J Spencer,Joseph Biederman,Pradeep G Bhide,Cheryl S Rosenfeld

doi:10.1371/journal.pone.0198064

Lin Zhang, Thomas J Spencer + Show 3 more

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https://doi.org/10.1371/journal.pone.0198064

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Abstract

BackgroundCigarette smoking by pregnant women is associated with a significant increase in the risk for cognitive disorders in their children. Preclinical models confirm this risk by showing that exposure of the developing brain to nicotine produces adverse behavioral outcomes. Here we describe behavioral phenotypes resulting from perinatal nicotine exposure in a mouse model, and discuss our findings in the context of findings from previously published studies using preclinical models of developmental nicotine exposure.Methodology/Principal findingsFemale C57Bl/6 mice received drinking water containing nicotine (100μg/ml) + saccharin (2%) starting 3 weeks prior to breeding and continuing throughout pregnancy, and until 3 weeks postpartum. Over the same period, female mice in two control groups received drinking water containing saccharin (2%) or plain drinking water. Offspring from each group were weaned at 3-weeks of age and subjected to behavioral analyses at 3 months of age. We examined spontaneous locomotor activity, anxiety-like behavior, spatial working memory, object based attention, recognition memory and impulsive-like behavior. We found significant deficits in attention and working memory only in male mice, and no significant changes in the other behavioral phenotypes in male or female mice. Exposure to saccharin alone did not produce significant changes in either sex.Conclusion/SignificanceThe perinatal nicotine exposure produced significant deficits in attention and working memory in a sex-dependent manner in that the male but not female offspring displayed these behaviors. These behavioral phenotypes are associated with attention deficit hyperactivity disorder (ADHD) and have been reported in other studies that used pre- or perinatal nicotine exposure. Therefore, we suggest that preclinical models of developmental nicotine exposure could be useful tools for modeling ADHD and related disorders.

Highlights

It is estimated that approximately 37 million American adults and 3 million American middle school and high school students smoke cigarettes [1]
We describe behavioral phenotypes resulting from perinatal nicotine exposure in a mouse model, and discuss our findings in the context of findings from previously published studies using preclinical models of developmental nicotine exposure
The developmental milestones are comparable to those in our previous studies of prenatal nicotine exposure, in which the offspring were cross-fostered to drug naïve dams on the day of birth [8, 15]

Summary

Introduction

It is estimated that approximately 37 million American adults and 3 million American middle school and high school students smoke cigarettes [1]. Preclinical studies [3,4,5,6,7,8,9] and clinical studies [10,11,12,13,14] show that prenatal nicotine exposure or cigarette smoking by pregnant women is associated with an increased risk of cognitive disabilities in their children. Cigarette smoking by pregnant women is associated with a significant increase in the risk for cognitive disorders in their children. Preclinical models confirm this risk by showing that exposure of the developing brain to nicotine produces adverse behavioral outcomes. We describe behavioral phenotypes resulting from perinatal nicotine exposure in a mouse model, and discuss our findings in the context of findings from previously published studies using preclinical models of developmental nicotine exposure

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