Abstract
Nicotine use in adolescence is pervasive in the United States and, according to the Gateway Hypothesis, may lead to progression towards other addictive substances. Given the prevalence of nicotine and ethanol comorbidity, it is difficult to ascertain if nicotine is a gateway drug for ethanol. Our study investigated the relationship between adolescent exposure to nicotine and whether this exposure alters subsequent alcohol seeking behavior. We hypothesized that rats exposed to nicotine beginning in adolescence would exhibit greater alcohol seeking behavior than non-exposed siblings. To test our hypothesis, beginning at P28, female rats were initially exposed to once daily nicotine (0.4 mg/kg, SC) or saline for 5 days. Following these five initial injections, animals were trained to nose-poke for sucrose reinforcement (10%, w/v), gradually increasing to sweetened ethanol (10% sucrose; 10% ethanol, w/v) on an FR5 reinforcement schedule. Nicotine injections were administered after the behavioral sessions to minimize acute effects of nicotine on operant self-administration. We measured the effects of nicotine exposure on the following aspects of ethanol seeking: self-administration, naltrexone (NTX)-induced decreases, habit-directed behavior, motivation, extinction and reinstatement. Nicotine exposure did not alter self-administration or the effectiveness of NTX to reduce alcohol seeking. Nicotine exposure blocked habit-directed ethanol seeking. Finally, nicotine did not alter extinction learning or cue-induced reinstatement to sweetened ethanol seeking. Our findings suggest that nicotine exposure outside the behavioral context does not escalate ethanol seeking. Further, the Gateway Hypothesis likely applies to scenarios in which nicotine is either self-administered or physiologically active during the behavioral session.
Highlights
Conventional cigarette use among youth is in steady decline; novel modes of consumption have arisen and are more readily available, potentially leading to increased levels of nicotine exposure
With apparent ease of access to nicotine and ethanol, the aim of this study was to determine if adolescents that are exposed to nicotine are more susceptible to escalate ethanol seeking
We first measured if nicotine exposure beginning during adolescence altered acquisition of operant self-administration of sweetened ethanol
Summary
Conventional cigarette use among youth is in steady decline; novel modes of consumption have arisen and are more readily available, potentially leading to increased levels of nicotine exposure. In 2016, according to the National Institutes of Health ‘‘Monitoring the Future Survey 2016’’, the percent of youth using conventional cigarettes in the past month among 8th, 10th and 12th grades was 2.6%, 4.9% and 10.5% respectively. E-cigarette use encompassed 6.2%, Adolescent Nicotine and Ethanol Seeking. 11.0% and 12.5% at the same grade level These statistics argue that consumption of nicotine by conventional tobacco sources, e-cigarettes, or smokeless tobacco may pose a health threat to the future of the youth in the United States. Alcohol use among adolescents is widespread, with over 35% of youth grades 8–12 in the United States reporting regular consumption and approximately 15% reporting heavy drinking or binge-drinking episodes (Bachman, 2002). With apparent ease of access to nicotine and ethanol, the aim of this study was to determine if adolescents that are exposed to nicotine are more susceptible to escalate ethanol seeking
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