Research reportPersistent and delayed behavioral changes after nicotine treatment in adolescent rats
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].
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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.
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2020, Food and Chemical ToxicologyCitation Excerpt :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).