BEHAVIORAL AND DOPAMINERGIC SENSITIZATION TO NICOTINE

对尼古丁的行为和多巴胺能敏感性

• 批准号: 7287658
• 负责人: Paul R Vezina
• 金额: $ 26.29万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287658
• 关键词: Acute; Affect; Amphetamines; Appetitive Behavior; Behavior; Behavioral; Brain; Brain Stem; Brain region; Cell Nucleus; Characteristics; Cholinergic Receptors; Chronic; Classification; Cocaine; Development; Dopamine; Dose; Drug Sensitization; Drug abuse; Drug usage; Epidemiologic Studies; Event; Exposure to; Future; Generations; Human; Individual; Intake; Knowledge; Laboratory Animals; Lead; Locomotion; Long-Term Effects; Measures; Mecamylamine; Midbrain structure; Molecular; Motivation; Motor Activity; Neurons; Neurotransmitters; Nicotine; Nucleus Accumbens; Numbers; Opiates; Pharmaceutical Preparations; Prosencephalon; Range; Rattus; Research Personnel; Risk; Role; Self Administration; Self-Administered; Site; System; Testing; Time; Tobacco; Treatment Protocols; Up-Regulation; Ventral Tegmental Area; Week; Withdrawal; Work; day; dopamine system; drug craving; drug seeking behavior; neuroadaptation; neurotransmission; prevent; programs; receptor; research study

Behavioral and dopaminergic sensitization by nicotine The aim of the following experiments is to determine how neuronal systems in brain are affected by chronic exposure to nicotine and to assess whether these effects can subsequently impact behaviors directed at obtaining the drug. Because nicotine, like other stimulants self-administered by rats and humans, is known to promote neurotransmission in the ascending midbrain dopamine (DA) systems, the proposed experiments will focus on this neurotransmitter known to be critical for the generation of appetitive behaviors such as locomotion and drug self-administration. Rats, like humans, will work to obtain nicotine. In addition, nicotine use is most often characterized by habitual, repeated intake over long periods of time. It is necessary therefore to gain a better understanding of the short- and long-term changes that are produced by prolonged exposure to the drug. This latter point is important because, while knowledge of the acute effects of nicotine on brain has increased somewhat, relatively little is known of the consequences for midbrain DA neurotransmission and the promotion of drug seeking behaviors of prolonged exposure to the drug either actively or passively. The following experiments will seek to elucidate these consequences by studying stimulant-induced locomotion, midbrain DA activation and self-administration in rats. Experiments in Aim 1 will characterize the effects of different nicotine exposure regimens on the induction of sensitization by nicotine. Those in Aim 2 will seek to identify the brain regions containing the nicotine acetylcholine receptor fields underlying the induction of sensitization. Finally, the impact of nicotine sensitization on the motivation to self-administer nicotine will be assessed in Aim 3. The results obtained will lead to a better understanding of the mechanisms underlying the pursuit of nicotine and the manner in which prolonged exposure to the drug may exacerbate drug-directed behaviors.

尼古丁的行为和多巴胺能致敏作用 以下实验的目的是确定大脑中的神经系统如何受到 长期暴露于尼古丁，并评估这些影响是否会随后影响行为 目的是获得药物。因为尼古丁，就像其他老鼠和人类自己服用的兴奋剂一样， 已知促进中脑多巴胺（DA）系统的神经传递， 实验将集中在这种已知对产生食欲行为至关重要的神经递质上 例如运动和药物自我给药。 老鼠和人类一样，会努力获得尼古丁。此外，尼古丁的使用最常见的特点是 长期习惯性重复摄入。因此，有必要更好地了解 长期暴露于药物所产生的短期和长期变化。后一点是 重要的是，虽然尼古丁对大脑的急性影响的知识有所增加， 对中脑DA神经传递和药物促进的后果知之甚少。 主动或被动地寻求长期暴露于药物的行为。以下实验 将通过研究兴奋剂诱导的运动、中脑DA激活来试图阐明这些结果 和大鼠自身给药。 目标1中的实验将表征不同尼古丁暴露方案对 尼古丁致敏诱导。目标2中的那些人将寻求识别包含 尼古丁乙酰胆碱受体领域潜在的敏化诱导。最后，尼古丁的影响 将在目标3中评估自我给予尼古丁动机的敏感性。 所获得的结果将有助于更好地理解追求 尼古丁以及长期暴露于药物可能加剧药物导向行为的方式。