Madayag Aric C, Czarnecki Kyle S, Wangler Lynde M, Robinson Donita L
Bowles Center for Alcohol Studies, University of North CarolinaChapel Hill, NC, United States.
Department of Pharmacology, University of North CarolinaChapel Hill, NC, United States.
Front Behav Neurosci. 2017 Aug 17;11:153. doi: 10.3389/fnbeh.2017.00153. eCollection 2017.
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.
在美国，青少年使用尼古丁的现象很普遍，根据通路假说，这可能会导致向其他成瘾物质发展。鉴于尼古丁和乙醇共病的普遍性，很难确定尼古丁是否是乙醇的通路药物。我们的研究调查了青少年接触尼古丁与这种接触是否会改变随后的觅酒行为之间的关系。我们假设从青春期开始接触尼古丁的大鼠比未接触的同胞表现出更强的觅酒行为。为了验证我们的假设，从出生后第28天开始，雌性大鼠最初每天接受一次尼古丁（0.4mg/kg，皮下注射）或生理盐水注射，持续5天。在这五次初始注射之后，动物被训练通过鼻触来获取蔗糖强化物（10%，w/v），并在固定比率5强化程序下逐渐增加到甜乙醇（10%蔗糖；10%乙醇，w/v）。尼古丁注射在行为训练后进行，以尽量减少尼古丁对操作性自我给药的急性影响。我们测量了尼古丁暴露对觅酒行为以下方面的影响：自我给药、纳曲酮（NTX）诱导的减少、习惯导向行为、动机、消退和恢复。尼古丁暴露并未改变自我给药或NTX减少觅酒行为效果。尼古丁暴露阻断了习惯导向的觅酒行为。最后，尼古丁并未改变消退学习或线索诱导的对甜乙醇觅求行为的恢复。我们的研究结果表明，行为情境之外的尼古丁暴露不会增加觅酒行为。此外，通路假说可能适用于尼古丁在行为训练期间是自我给药或具有生理活性的情况。
