Murray Jennifer E, Walker Andrew W, Polewan Robert J, Bevins Rick A
Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA.
Psychopharmacology (Berl). 2011 Jan;213(1):131-41. doi: 10.1007/s00213-010-2022-5. Epub 2010 Sep 22.
Research using a drug discriminated goal-tracking (DGT) task showed that the N-methyl-D: -aspartate (NMDA) channel blocker MK-801 (dizocilpine) reduced the nicotine-evoked conditioned response (CR).
Given the unknown mechanism of the effect, Experiment 1 replicated the MK-801 results and included tests with NMDA receptor ligands. Experiments 2a and 2b tested whether MK-801 pretreatment blocked DGT via a state-dependency effect.
In Experiment 1, adult male Sprague-Dawley rats received intermittent access to liquid sucrose following nicotine (0.4 mg base/kg); no sucrose was delivered on intermixed saline sessions. Conditioning was indicated by increased anticipatory dipper entries (goal-tracking) on nicotine compared to saline sessions. Antagonism and/or substitution tests were conducted with MK-801, phencyclidine, CGP 39551, d-CPPene (SDZ EAA 494), Ro 25,6981, L-701,324, ACPC, and NMDA. In Experiment 2a, rats received nicotine and sucrose on every session-no intermixed saline sessions without sucrose. Tests combined MK-801 or the non-competitive nicotinic acetylcholine receptor antagonist, mecamylamine with either nicotine or saline. Experiment 2b had sucrose delivered on saline sessions and no sucrose on intermixed nicotine sessions followed by MK-801 antagonism tests of the saline CS.
MK-801 and phencyclidine dose-dependently attenuated the CR in Experiment 1. Ro-25,6981 enhanced the CR, but did not substitute for nicotine. Other ligands showed inconsistent effects. In Experiment 2a, MK-801 pretreatment reduced goal-tracking when given before nicotine and saline test sessions; mecamylamine pretreatment had no effect. In Experiment 2b, MK-801 dose-dependently attenuated the saline-evoked CR.
Combined, the results suggest that MK-801 blocks discriminated goal-tracking by virtue of state-changing properties.
使用药物辨别性目标追踪（DGT）任务的研究表明，N-甲基-D-天冬氨酸（NMDA）通道阻滞剂MK-801（地佐环平）可降低尼古丁诱发的条件反应（CR）。
鉴于该效应的机制尚不清楚，实验1重复了MK-801的实验结果，并纳入了NMDA受体配体的测试。实验2a和2b测试了MK-801预处理是否通过状态依赖性效应阻断DGT。
在实验1中，成年雄性Sprague-Dawley大鼠在给予尼古丁（0.4mg碱/kg）后间歇性接触液体蔗糖；在混合盐水实验中不给予蔗糖。与盐水实验相比，尼古丁实验中预期舔舐次数增加（目标追踪）表明形成了条件反射。用MK-801、苯环利定、CGP 39551、d-CPPene（SDZ EAA 494）、Ro 25,6981、L-701,324、ACPC和NMDA进行拮抗和/或替代测试。在实验2a中，大鼠每次实验都给予尼古丁和蔗糖，没有不给予蔗糖的混合盐水实验。测试将MK-801或非竞争性烟碱型乙酰胆碱受体拮抗剂美加明与尼古丁或盐水联合使用。实验2b在盐水实验中给予蔗糖，在混合尼古丁实验中不给予蔗糖，然后对盐水条件刺激进行MK-801拮抗测试。
在实验1中，MK-801和苯环利定剂量依赖性地减弱了条件反应。Ro-25,6981增强了条件反应，但不能替代尼古丁。其他配体显示出不一致的效应。在实验2a中，MK-801预处理在尼古丁和盐水测试实验前给予时可减少目标追踪；美加明预处理没有效果。在实验2b中，MK-801剂量依赖性地减弱了盐水诱发的条件反应。
综合来看，结果表明MK-801凭借其改变状态的特性阻断辨别性目标追踪。
