DOI
https://doi.org/10.25772/2BTY-F448
Defense Date
2010
Document Type
Thesis
Degree Name
Master of Science
Department
Pharmacology & Toxicology
First Advisor
M. Imad Damaj
Abstract
Nicotine is one of the first and most commonly abused drugs in adolescence. According to The Center for Disease Control, every day more than 6000 adolescents try their first cigarette and over 3000 of them become daily smokers. Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. A number of studies has suggests that adolescents pre-exposed to nicotine may suffer permanent disruption of the brain’s reward systems through changes in dopamine receptor function. We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the likelihood of cocaine use in adulthood. Furthermore, it activates a neurobiological mechanism that is shared by many drugs of abuse, which will increase susceptibility to their rewarding effects. The work in this thesis contributes to the further understanding of this critical developmental period. Conditioned-place-preference, acute locomotor and locomotor sensitization pardigms were used to examine changes in cocaine sensitivity in adulthood. Testing was performed on adult ICR mice that were exposed to nicotine (0.1 or 0.5 mg/kg, S.C., b.i.d.) or saline during adolescence (postnatal days 28 or 46) or adult (postnatal day 70). Data showed that a 7-day exposure to the higher dose of nicotine (0.5 mg/kg) altered cocaine-induced responses. In contrast, neither 1 day exposure nor a low dose of nicotine (0.1 mg/kg) elicited this effect. A follow-up study was undertaken to determine if this enhancement generally applies to other drugs of abuse. Pre-exposure to 0.5mg/kg nicotine during early adolescence demonstrated significant enhancement to morphine reward, but it failed to increase d-amphetamine preference in a CPP model. Further research will be required in order to more fully examine the mechanisms of action for the observed changes in cocaine rewards. In summary, these findings suggest that early adolescent nicotine exposure leads to changes in cocaine reward and sensitivity during adulthood in both dose and duration matters. Indeed, the adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent drug reward.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
August 2010