Liu Xiu, Koren Andrei O, Yee Susan K, Pechnick Robert N, Poland Russell E, London Edythe D
Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Neuroreport. 2003 Aug 6;14(11):1503-5. doi: 10.1097/00001756-200308060-00020.
It is widely accepted that nicotine is the active ingredient of tobacco smoke that promotes tobacco dependence. Nicotine interacts with several subtypes of nicotinic acetylcholine receptors (nAChRs). In brain, it primarily targets nAChRs that contain beta2 and alpha4 subunits in combination and those composed of solely alpha7 subunits. The present study tested whether operantly trained rats would self-administer a ligand active at beta2-containing (i.e. not alpha7) nAChRs. Male Sprague-Dawley rats were trained to lever press for i.v. cocaine self-administration. After 2 weeks of cocaine washout, rats were given operant access to 5-iodo-A-85380 (5IA), a beta2-selective nAChR ligand, in daily 1 h sessions. The rats rapidly developed a stable level of 5IA self-administration behavior (unit dose = 5 nmol/kg/infusion). This finding suggests that interaction with beta2-containing nAChRs, without direct involvement of alpha7 receptors, can produce reinforcement and thereby can support self-administration behavior.
人们普遍认为尼古丁是烟草烟雾中导致烟草依赖的活性成分。尼古丁与多种烟碱型乙酰胆碱受体（nAChRs）亚型相互作用。在大脑中，它主要作用于含有β2和α4亚基组合的nAChRs以及仅由α7亚基组成的nAChRs。本研究测试了经过操作性训练的大鼠是否会自行给药一种对含β2（即不含α7）的nAChRs有活性的配体。雄性Sprague-Dawley大鼠经过训练，通过按压杠杆自行静脉注射可卡因。在停用可卡因2周后，大鼠每天有1小时的时间可以通过操作性方式获取5-碘-A-85380（5IA），一种β2选择性nAChR配体。大鼠迅速形成了稳定水平的5IA自行给药行为（单位剂量=5 nmol/kg/输注）。这一发现表明，与含β2的nAChRs相互作用，而无需α7受体的直接参与，即可产生强化作用，从而支持自行给药行为。
