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Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2017)

Cigarette smoking is the leading preventable cause of death in the United States. Of those who smoke, 9 out of 10 report trying their first cigarette before the age of 18. Although most people who initiate tobacco use are teenagers, animal models for studying tobacco dependence have traditionally focused on how adult animals initiate, withdrawal from and relapse to cigarette smoking. Furthermore, cigarette smoke contains more than 7,000 constituents, including nicotine, yet pre-clinical research has focused on nicotine alone. Our lab began studying these constituents by creating cigarette smoke extract, CSE, a solution which contains the aqueous constituents present in cigarette smoke. Previous work from our lab found that CSE is more potent than nicotine alone and can enhance stress-induced reinstatement in adult male rats. In order to understand how the presence of tobacco smoke constituents may affect adolescents, I investigated the role of these constituents in models of smoking initiation and relapse. I found that the tobacco smoke constituents did not influence adolescent or adult acquisition of self-administration. Adolescents self-administered more low-dose nicotine than adults when their increased non-specific responding was corrected for. During reinstatement of drug seeking, I found that CSE enhanced stress- + cue-induced reinstatement of drug-seeking behavior with no effect of age. To investigate the role of tobacco smoke constituents on attenuation of adolescent self-administration, a novel smoking cessation pharmacotherapy, AT-1001, which is a selective α3β4 nAChR functional antagonist, was used. AT-1001 attenuated both CSE and nicotine self-administration in adolescent rats to a similar degree. My results suggest that both age and the presence of tobacco smoke constituents are important factors in establishing a proper model of tobacco dependence. Furthermore, my findings provide novel insights on adolescent initiation and relapse and offer an exciting potential for the development of a new tobacco dependence animal model that could help create innovative therapeutics to curb the addiction faced by many.

    Cover page: Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2016)
    Although smoking initiation typically occurs during adolescence, most preclinical studies of tobacco use involve adult animals. Furthermore, their focus is largely on nicotine alone, even though cigarette smoke contains thousands of constituents. The present study therefore aimed to determine whether aqueous constituents in cigarette smoke affect acquisition of nicotine self-administration during adolescence in rats. Adolescent and adult male rats, aged postnatal day (P) 25 and 85, respectively, were food trained on a fixed ratio 1 (FR1) schedule, then allowed to self-administer one of 5 doses of nicotine (0, 3.75, 7.5, 15, or 30 μg/kg) or aqueous cigarette smoke extract (CSE) with equivalent nicotine content. Three progressively more difficult schedules of reinforcement, FR1, FR2, and FR5, were used. Both adolescent and adult rats acquired self-administration of nicotine and CSE. Nicotine and CSE similarly increased non-reinforced responding in adolescents, leading to enhanced overall drug intake as compared to adults. When data were corrected for age-dependent alterations in non-reinforced responding, adolescents responded more for low doses of nicotine and CSE than adults at the FR1 reinforcement schedule. No differences in adolescent responding for the two drugs were seen at this schedule, whereas adults had fewer responses for CSE than for nicotine. However, when the reinforcement schedule was increased to FR5, animals dose-dependently self-administered both nicotine and CSE, but no drug or age differences were observed. These data suggest that non-nicotine tobacco smoke constituents do not influence the reinforcing effect of nicotine in adolescents.
      Cover page: Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2023)

      Introduction

      Given the rapid increase in teen vaping over recent years it is critical to understand mechanisms underlying addiction and relapse to tobacco use at this age. To evaluate the role of non-nicotine constituents in cigarette smoke, our lab has previously established a model of intravenous self-administration of aqueous cigarette smoke extract (CSE). We now compare the sensitivity of male adolescent and adult rats who have self-administered CSE or nicotine to reinstatement with the pharmacological stressor, yohimbine, with and without cues.

      Methods

      Adolescents and adults, aged postnatal day (P) 34 and 84, were tested for the effect of yohimbine (0-2.5 mg/kg) on plasma corticosterone levels to establish a dose that was an effective stressor at both ages. Separate groups of animals were trained to lever press for food before beginning 1-hour drug self-administration sessions for nicotine or CSE (15 μg/kg/infusion nicotine content). Once stable responding was reached, drug was removed, and behavior extinguished. Drug-seeking behavior was reinstated with yohimbine, cues, or a combination of yohimbine and cues.

      Results

      Although adolescents and adults showed different dose-responses for yohimbine-induced corticosterone release, a dose of 2.5 mg/kg increased stress hormone levels at both ages. Whereas both ages displayed similar responding for CSE and nicotine, adolescents self-administered more CSE and nicotine as compared to adults. Cues and cues + stress reinstated responding to a greater extent in animals that had self-administered CSE, regardless of age.

      Discussion

      These findings suggest that non-nicotine tobacco smoke constituents influence later but not earlier stages of addiction in both adolescent and adult male rats.
        Cover page: Impact of tobacco smoke constituents on nicotine-seeking behavior in adolescent and adult male ratsCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2016)
        Animal models are used to study many human diseases, one of which is tobacco addiction. Most preclinical models use nicotine alone, although there are >7000 constituents present in tobacco smoke. The clinical literature suggests that cigarettes have a strong addictive potential, which is not paralleled in preclinical studies using nicotine alone. In order to address the gap between clinical and preclinical literature on tobacco dependence, cigarette smoke extracts containing tobacco constituents have been developed. This unit describes a procedure for producing an aqueous cigarette smoke extract (CSE) which animals readily self-administer. In addition, we describe how to make the apparatus for producing CSE and how to analyze the solution for nicotine content. © 2016 by John Wiley & Sons, Inc.
          Cover page: Cigarette Smoke Extract: A Preclinical Model of Tobacco Dependence
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