Understanding and mitigating exacerbated nicotine use resulting from Pavlovianinteroceptive conditioning

了解和缓解巴甫洛夫内感受调节导致的尼古丁使用加剧

• 批准号: 10736191
• 负责人: Rick A Bevins
• 金额: $ 35.98万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736191
• 关键词: Address; Alcohols; Association Learning; Basic Science; Biological; Biology; Chronic; Clinical; Desire for food; Development; Dose; Environmental Risk Factor; Failure; Female; Foundations; Friends; Goals; Health; Health Personnel; Heart Diseases; Heart Rate; Incubated; Individual; Intake; Intravenous; Learning; Literature; Location; Malignant Neoplasms; Methodology; Nicotine; Nicotine Dependence; Nicotine Use Disorder; Outcome; Pharmaceutical Preparations; Pre-Clinical Model; Process; Rattus; Recording of previous events; Relapse; Research; Research Personnel; Rewards; Rodent; Role; Science; Scientific Advances and Accomplishments; Scientist; Self Administration; Sex Differences; Smell Perception; Smoker; Smoking; Societies; Stimulus; Stress; Sucrose; Taste Perception; Testing; Theoretical model; Time; Tobacco; Tobacco use; Translating; Woman; Work; combustible tobacco; conditioning; drug abstinence; drug seeking behavior; economic cost; electronic liquid; forgetting; improved; innovation; interest; male; men; nicotine cessation; nicotine replacement; nicotine self-administration; nicotine use; novel strategies; peer; pharmacologic; prevent; programs; reinforcer; sex; sociocultural determinant; vaper; vaping; visual stimulus

PROJECT ABSTRACT Nicotine is the primary addictive constituent in tobacco. For an individual, chronic tobacco use is associated with a significant increase in heart disease and many forms of cancer. Increasingly, researchers are documenting health issues associated with vaping flavored e-juice containing nicotine. There are some important sex differences in chronic nicotine use and its health consequences. Women on average are impacted more by environmental and sociocultural factors, take less time to become nicotine dependent, make fewer attempts to quit, abstain for less time, relapse at higher rates, and benefit less from nicotine replacement therapy. Enormous gains to the individual and society would come from a more complete understanding of factors that contribute to nicotine use and misuse. Through Pavlovian conditioning processes, environmental stimuli associated with drugs such as nicotine can become powerful modulators of drug-seeking behavior. Another related and important factor in the development of chronic nicotine use is the pharmacological effects of nicotine serving as an internal (interoceptive) stimulus that enters into a conditioned association with other reinforcers (e.g., peer acceptance, alcohol, work breaks, stress relief, etc.). Thus, smokers/vapers over time develop a rich interoceptive conditioning history with the stimulus effects of nicotine. Our long-term objective is to understand how this conditioning history alters the trajectory of use and misuse in individuals and, in doing so, provide new clues on how to improve cessation programs. To this end, we recently developed an innovative new approach using rats that merges interoceptive conditioning of intravenous (IV) nicotine with its later self-administration. When IV nicotine is repeatedly paired with an appetitive reinforcer (i.e., sucrose), this conditioning history dose- and sex- dependently increases nicotine self-administration (21 to 126%)—an effect more profound in female rats. Leveraging the methodological strengths of this new approach, we address three Aims in the present proposal. Aim 1 will assess whether the need to recall the learning after a retention interval alters the strength of the conditioned reinforcing effects of nicotine. Aim 2 will determine whether the addition of a weak reinforcer during self-administration interacts with nicotine and its newly acquired conditioned reinforcing effects. Aim 3 will examine whether an external (exteroceptive) stimulus will compete with the interoceptive nicotine stimulus for conditioned reinforcing value, thus weakening its later impact on nicotine intake. A fundamental understanding of such factors that influence the effect of interoceptive conditioning with nicotine will refine and advance our theoretical models. These advancements will provide foundational research for other basic scientists and clues for clinical scientists and healthcare providers working to improve approaches to treating nicotine use disorder.

项目摘要