File Sandra E, Cheeta Survjit, Irvine Elaine E, Tucci Sonia, Akthar Morium
Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, London SE1 1UL, UK.
Psychopharmacology (Berl). 2002 Nov;164(3):309-17. doi: 10.1007/s00213-002-1219-7. Epub 2002 Sep 5.
Despite its reinforcing properties nicotine has also been reported to produce anxiety in humans and anxiogenic effects in animal tests of anxiety.
The aims of this study were three-fold: (a) to investigate whether anxiety can be conditioned to cues associated with an acute anxiogenic dose of nicotine, (b) to investigate whether the conditioned anxiety is specific to a particular test of anxiety, and (c) to investigate whether nicotine pre-exposure influences the development of a conditioned anxiogenic effect.
An anxiogenic dose of nicotine was administered to rats either before or after experience with the social interaction (SI) test. The retention of a conditioned anxiogenic response was examined when the rats were re-tested undrugged in the SI test 24 h later. To test whether conditioned anxiety was test specific, rats that had been tested in the elevated plus-maze with an anxiogenic dose of nicotine were retested undrugged in the SI test 24 h later, and vice versa. We then examined the effects of 4 days or 4 weeks pre-exposure to nicotine on the development of a conditioned anxiogenic response in the SI test.
Rats injected with nicotine (0.45 mg/kg s.c.) 5 min before the social interaction test spent significantly less time in SI, indicating an unconditioned anxiogenic effect than did vehicle-injected controls or rats injected with nicotine after the test. After 24 h when all groups were tested undrugged only those previously tested in SI after nicotine injection showed a significant conditioned anxiogenic effect. This conditioned anxiety was test specific. Rats injected with nicotine before the SI test did not show an anxiogenic response when tested 24 h later undrugged in the plus-maze, and vice versa. Furthermore, although 4 days exposure to nicotine (0.45 mg/kg s.c.) did not prevent the development of a conditioned anxiogenic response, 4 weeks self-administration of nicotine (total dose, 0.45 mg/kg i.v) in an operant chamber did not affect the acute anxiogenic response to nicotine in the SI test, but it did prevent the development of conditioned anxiety.
The present findings suggest that anxiety can be conditioned following exposure to an anxiogenic dose of nicotine, and that this anxiety is specific to the contextual cues associated with the SI test.
尽管尼古丁具有强化特性，但也有报道称其会在人类中引发焦虑，并在动物焦虑测试中产生致焦虑作用。
本研究的目的有三个方面：(a) 研究焦虑是否可以与急性致焦虑剂量的尼古丁相关线索建立条件反射，(b) 研究条件性焦虑是否特定于某一特定焦虑测试，(c) 研究尼古丁预暴露是否会影响条件性致焦虑效应的发展。
在大鼠进行社交互动（SI）测试之前或之后给予其致焦虑剂量的尼古丁。24小时后，当大鼠在未用药的情况下再次进行SI测试时，检查条件性致焦虑反应的保持情况。为了测试条件性焦虑是否具有测试特异性，在高架十字迷宫中用致焦虑剂量的尼古丁进行测试的大鼠，24小时后在未用药的情况下再次进行SI测试，反之亦然。然后，我们研究了尼古丁预暴露4天或4周对SI测试中条件性致焦虑反应发展的影响。
在社交互动测试前5分钟注射尼古丁（0.45毫克/千克皮下注射）的大鼠在SI中的时间显著少于注射溶剂的对照组或测试后注射尼古丁的大鼠，表明存在非条件性致焦虑效应。24小时后，当所有组在未用药的情况下进行测试时，只有之前在注射尼古丁后进行SI测试的组表现出显著的条件性致焦虑效应。这种条件性焦虑具有测试特异性。在SI测试前注射尼古丁的大鼠在24小时后未用药时在高架十字迷宫中测试未表现出致焦虑反应，反之亦然。此外，尽管暴露于尼古丁（0.45毫克/千克皮下注射）4天并不能阻止条件性致焦虑反应的发展，但在操作性条件反射箱中尼古丁自我给药4周（总剂量，0.45毫克/千克静脉注射）并不影响SI测试中对尼古丁的急性致焦虑反应，但确实阻止了条件性焦虑的发展。
目前的研究结果表明，暴露于致焦虑剂量的尼古丁后焦虑可以形成条件反射，并且这种焦虑特定于与SI测试相关的情境线索。
