Mundy W R, Iwamoto E T
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington 40536.
Psychopharmacology (Berl). 1988;94(2):267-74. doi: 10.1007/BF00176858.
Experimentally naive male, Sprague-Dawley rats maintained at 85% of their original body weight were trained to touch a retractable lever that was presented on a random interval 48-s schedule. The lever retracted when touched or after 15 s had elapsed, and one 45 mg food pellet was delivered simultaneously with lever retraction or after an 8-s delay. Rats received ten daily sessions each consisting of ten lever presentations. Nicotine (0.25-0.8 mg/kg SC) administration, either 15 min prior to (pre-session) or immediately after (post-session) the daily autoshaping sessions, caused a significant dose-related impairment of acquisition with the post-session injections having the greater effect. Low doses of nicotine (0.025-0.1 mg/kg SC) had little effect on acquisition when injected pre-session or post-session. Injections of 0.45 mg/kg nicotine either immediately (t = 0) or at +5 min after the daily sessions impaired acquisition of the lever-touch response. Nicotine injected at +15, +30, +60, or +120 min had no effect on acquisition. A single intraventricular injection of the ganglionic blocker chlorisondamine (5 micrograms) 2 weeks prior to autoshaping blocked the impairment produced by 0.45 mg/kg nicotine. Post-session injections of nicotine did not alter the lever-touch behavior of well-trained animals, but suppressed responding in animals that were partially trained. Thus, nicotine-induced impairment of the autoshaped lever-touch response is dose dependent, centrally mediated, occurs within 5 min of a SC injection, and may interfere with post-training consolidation processes.
将体重维持在原始体重85%的未经实验的雄性斯普拉格-道利大鼠训练至触碰以随机间隔48秒呈现的可伸缩杠杆。杠杆在被触碰时或15秒过去后缩回,同时在杠杆缩回时或延迟8秒后给予一粒45毫克的食物颗粒。大鼠每天接受十次训练,每次训练包含十次杠杆呈现。在每日自动成型训练前15分钟(训练前)或训练后立即(训练后)皮下注射尼古丁(0.25 - 0.8毫克/千克),会导致与剂量相关的显著习得障碍,训练后注射的影响更大。低剂量尼古丁(0.025 - 0.1毫克/千克皮下注射)在训练前或训练后注射时对习得影响很小。在每日训练后立即(t = 0)或+5分钟时注射0.45毫克/千克尼古丁会损害杠杆触碰反应的习得。在+15、+30、+60或+120分钟时注射尼古丁对习得没有影响。在自动成型训练前两周脑室内单次注射神经节阻滞剂氯筒箭毒碱(5微克)可阻断0.45毫克/千克尼古丁产生的损害。训练后注射尼古丁不会改变训练良好动物的杠杆触碰行为,但会抑制部分训练动物的反应。因此,尼古丁诱导的自动成型杠杆触碰反应损害是剂量依赖性的,由中枢介导,在皮下注射后5分钟内发生,并且可能干扰训练后的巩固过程。