Elsevier

Brain Research

Volume 880, Issues 1–2, 13 October 2000, Pages 167-172
Brain Research

Research report
Persistent and delayed behavioral changes after nicotine treatment in adolescent rats

https://doi.org/10.1016/S0006-8993(00)02823-7Get rights and content

Abstract

Despite the increasing use of tobacco by adolescents, few animal studies have addressed the neurobehavioral consequences of nicotine exposure during this period. We administered nicotine to adolescent rats via continuous infusion on postnatal days (PN) 30 through 47.5, using a dosage regimen that maintains plasma levels similar to those found in smokers or in users of the transdermal nicotine patch. Behavior in a novel open field and learning a passive avoidance task were assessed during nicotine treatment and for 2 weeks post-treatment. On PN44, during nicotine exposure, female rats showed decreased grooming, an effect not seen in males; this effect is opposite to the effects of nicotine in adult rats. Two weeks after cessation of nicotine administration, females showed deficits in locomotor activity and rearing, whereas males again were unaffected; the behavioral deficits appeared at the same age at which gender-selective brain cell damage emerges. In contrast, nicotine exposure enhanced passive avoidance, with the effect intensifying and persisting throughout the post-treatment period. These results reinforce the concept that developmental vulnerability to nicotine extends into adolescence, with patterns of drug effects different from those in earlier or later periods. The correlation of neurochemical with behavioral effects strengthens the connection between adolescent nicotine exposure and persistent functional changes that may influence drug habituation, learning and memory.

Introduction

Recent estimates indicate that over one-third of U.S. high school students are using tobacco products and that nearly 3000 children under the age of 18 begin smoking every day [20]. Early initiation of smoking leads to higher daily consumption of cigarettes and a reduced probability of quitting [4], [22], [24]. Most life-long smokers begin their habit as adolescents [20], [22] and it is therefore somewhat surprising that relatively little attention has been paid to establishing animal models of adolescent nicotine exposure. Recently, we found that adolescent rats given nicotine show gender-selective, persistent changes in nicotinic receptor expression, accompanied by brain cell loss [35], hippocampal damage that appears after several weeks’ delay [34], [35], and persistent changes in cholinergic synaptic activity, particularly in the hippocampus [33]. Initial behavioral studies with adolescent nicotine exposure also found long-term changes in the learning related to reward tasks [14] but there have been no systematic evaluations of behavioral performance in the period during and immediately after adolescent nicotine administration.

Accordingly, the current study examines the effects of adolescent nicotine exposure on two sets of behaviors known to be affected by nicotine administration in adults: open field behaviors (locomotion, rearing, grooming) [3], [5], [13], [36] and passive avoidance [23], [29], [37]. Nicotinic cholinergic pathways are essential in the acquisition of passive avoidance behaviors [19] and hippocampal cholinergic pathways are specifically involved [1]. We used an established minipump infusion model that produces and maintains plasma nicotine levels within the range seen in typical smokers or in users of the nicotine transdermal patch and that, in the adolescent brain produces the biochemical changes already described [33], [34], [35].

Section snippets

Animal treatments

All studies were carried out in accordance with the declaration of Helsinki and with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institutes of Health. Litters of Sprague–Dawley rats (Zivic Laboratories, Pittsburgh, PA) were shipped with their dams by climate-controlled truck (total transit time less than 12 h). At weaning, postnatal day (PN) 21, animals were housed individually and allowed free access to food and water. Drug treatments were

Results

Global statistical analyses (Table 1) across all three open field behaviors indicated significant main effects of gender and significant differences among the measures (main effect of measure). In terms of the effects of nicotine administration, there were age-related treatment effects that were distinct for each of the divers measures (interaction of treatment×age×measure). In addition, the actions of nicotine were gender-selective, as indicated by an interaction of

Discussion

The current study demonstrates that the neurochemical changes evoked by adolescent nicotine exposure [33], [34], [35] are indeed accompanied by both immediate and delayed behavioral alterations. Interestingly, we observed gender-selective effects in behaviors in an open field, with females affected to a greater extent than males: during nicotine exposure, females showed reduced grooming, and at PN60, 2 weeks after cessation of nicotine exposure, these animals also displayed reduced locomotion

Acknowledgements

Supported by a grant from the Smokeless Tobacco Research Council and by a STAR fellowship from the US Environmental Protection Agency.

References (37)

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    Therefore, nicotine is able to increase neuronal activity with a greater effect in the adolescent brain when compared to the adult (Ehlinger et al., 2016; Shram et al., 2007). Furthermore, chronic nicotine exposure during adolescence has long-term consequences on cognitive behavior associated with diminished cognitive function, which could lead to reduced attention span and enhanced impulsivity in adults (Counotte et al., 2009, 2011; Trauth et al., 2000). EC associated nicotine exposure during adolescence leads to aberrant activation of nAChRs, and further lifelong changes in neuronal signaling, influencing behaviors such as addiction, cognition and emotional regulation (Tobore, 2019; Yuan et al., 2015).

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