LeSage Mark G, Burroughs Danielle, Dufek Matthew, Keyler Daniel E, Pentel Paul R
Minneapolis Medical Research Foundation, 914 South 8th Street, D3-860, Minneapolis, MN 55404, USA.
Pharmacol Biochem Behav. 2004 Nov;79(3):507-13. doi: 10.1016/j.pbb.2004.09.002.
The objective of the present study was to determine the relative efficacy of nicotine priming and nicotine-paired stimuli in reinstating extinguished NSA in rats. The relative efficacy of different stimulus conditions in reinstating NSA was also determined. Rats were trained to self-administer nicotine (0.03 mg/kg/inf) under an FR 5 schedule. Onset of a light above the active lever was correlated with nicotine availability, while offset of the light was paired with each nicotine infusion. In Experiment 1, saline extinction was arranged in the presence of these light stimuli. After extinction criteria were met, the effects of priming doses of nicotine (0.01, 0.03. and 0.06 mg/kg/inf, i.v.) on active lever pressing were determined. In Experiment 2, extinction of NSA was arranged in the absence of the light stimuli. After extinction criteria were met, reinstatement sessions were arranged involving either (1) a priming infusion of nicotine (0.03 mg/kg), (2) presentation of the same light stimuli as during NSA training, (3) constant illumination of the cue light, or (4) a combination of a nicotine priming infusion with one of the stimulus-light conditions. In Experiment 1, nicotine generally failed to reinstate NSA at any priming dose. In Experiment 2, both stimulus conditions reinstated NSA, with the stimulus condition identical to training producing a greater effect. Nicotine priming alone failed to significantly reinstate NSA. Nicotine priming combined with either stimulus condition was no more effective than each stimulus condition alone in reinstating NSA. These findings suggest that nicotine-paired cues are more effective than nicotine alone in reinstating extinguished NSA and are consistent with other studies showing that nicotine-paired stimuli play an important role in the reacquisition of NSA.
本研究的目的是确定尼古丁启动和尼古丁配对刺激在恢复大鼠消退的尼古丁自我给药行为(NSA)方面的相对效力。还确定了不同刺激条件在恢复NSA方面的相对效力。大鼠在固定比率为5的给药方案下接受训练,自行注射尼古丁(0.03毫克/千克/次)。活动杠杆上方的灯光亮起与尼古丁可得性相关,而灯光熄灭则与每次尼古丁注射配对。在实验1中,在这些灯光刺激存在的情况下安排生理盐水消退。达到消退标准后,确定尼古丁启动剂量(0.01、0.03和0.06毫克/千克/次,静脉注射)对活动杠杆按压的影响。在实验2中,在没有灯光刺激的情况下安排NSA消退。达到消退标准后,安排恢复实验,包括(1)一次尼古丁启动注射(0.03毫克/千克),(2)呈现与NSA训练期间相同的灯光刺激,(3)提示灯光持续照明,或(4)尼古丁启动注射与一种刺激灯光条件的组合。在实验1中,任何启动剂量的尼古丁通常都未能恢复NSA。在实验2中,两种刺激条件都恢复了NSA,与训练相同的刺激条件产生了更大的效果。单独的尼古丁启动未能显著恢复NSA。尼古丁启动与任何一种刺激条件相结合在恢复NSA方面并不比单独的每种刺激条件更有效。这些发现表明,尼古丁配对线索在恢复消退的NSA方面比单独的尼古丁更有效,并且与其他研究一致,这些研究表明尼古丁配对刺激在NSA的重新习得中起重要作用。