BEHAVIORAL AND DOPAMINERGIC SENSITIZATION TO NICOTINE

尼古丁的行为敏化和多巴胺能敏化 以下实验的目的是确定大脑中的神经元系统是如何受到 长期接触尼古丁，并评估这些影响是否会随后影响行为 目的是为了获得药物。因为尼古丁，就像其他由老鼠和人类自己服用的兴奋剂一样， 已知可促进中脑多巴胺(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。 如运动和药物自我给药。 老鼠和人类一样，会努力获取尼古丁。此外，尼古丁的使用最常见的特征是 习惯性的，重复的长时间摄入。因此，有必要更好地了解 长期接触药物所产生的短期和长期变化。后一点是 重要的是，尽管关于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影响知之甚少 主动或被动地寻找长期接触药物的行为。下面的实验 将试图通过研究兴奋剂诱导的运动、中脑DA激活来阐明这些后果 和大鼠的自我给药。 目标1中的实验将表征不同尼古丁暴露方案对 尼古丁的致敏作用。那些在目标2中的人将试图识别包含 尼古丁-乙酰胆碱受体区域是敏化诱导的基础。最后，尼古丁的影响 将在目标3中评估对自我管理尼古丁的动机的敏感化。 所获得的结果将有助于更好地理解追求 尼古丁和长期接触这种药物可能会加剧药物导向行为的方式。

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.