Le Foll Bernard, Goldberg Steven R
Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 2005 Apr;178(4):481-92. doi: 10.1007/s00213-004-2021-5. Epub 2004 Nov 18.
Conditioned place preference (CPP) procedures provide one measure of potential rewarding effects of abused drugs. Many attempts to induce CPP with nicotine have been unsuccessful.
To assess the influence of nicotine dose and stimulus assignment procedure on development of nicotine-induced CPP.
Initial preferences for one side of a two-compartment apparatus were first determined in Sprague-Dawley rats. In subsequent conditioning trials, the compartment paired with nicotine was the initially preferred side for half of the rats, and the initially non-preferred side for the other half. Rats received either an injection of nicotine (0.01-2 mg/kg SC) before being placed in one compartment (three trials) or saline before being placed in the other compartment (three trials). Control rats had saline injections associated with both compartments. A final test trial with no injection assessed final place preference.
Significant CPP were induced by 0.1-1.4 mg/kg doses of nicotine. Nicotine-induced CPP were only apparent when nicotine was paired with the initially non-preferred side. Moreover, a very high dose of nicotine (2 mg/kg) induced conditioned place aversion when paired with the initially preferred side of the apparatus.
Nicotine induced significant CPP across a wide range of doses, in accordance with its role as the primary addictive component of tobacco. Small preferences for one side of the apparatus played a major role in the development of nicotine-induced CPP. These findings suggest that biased procedures may be more suitable than unbiased procedures for evaluation of rewarding effects of nicotine using CPP paradigms.
条件性位置偏爱(CPP)程序提供了一种衡量滥用药物潜在奖赏效应的方法。许多用尼古丁诱导CPP的尝试都未成功。
评估尼古丁剂量和刺激分配程序对尼古丁诱导的CPP发展的影响。
首先在斯普拉格-道利大鼠中确定其对两室装置一侧的初始偏爱。在随后的条件试验中,与尼古丁配对的隔室对一半大鼠来说是最初偏爱的一侧,而对另一半大鼠来说是最初不偏爱的一侧。大鼠在被放入一个隔室之前接受尼古丁注射(0.01 - 2毫克/千克,皮下注射)(三次试验),或者在被放入另一个隔室之前接受生理盐水注射(三次试验)。对照大鼠在两个隔室都接受生理盐水注射。最后一次无注射的测试试验评估最终的位置偏爱。
0.1 - 1.4毫克/千克剂量的尼古丁诱导出显著的CPP。仅当尼古丁与最初不偏爱的一侧配对时,尼古丁诱导的CPP才明显。此外,当与装置最初偏爱的一侧配对时,非常高剂量的尼古丁(2毫克/千克)诱导出条件性位置厌恶。
尼古丁在很宽的剂量范围内诱导出显著的CPP,这与其作为烟草主要成瘾成分的作用一致。对装置一侧的小偏爱在尼古丁诱导的CPP发展中起主要作用。这些发现表明,对于使用CPP范式评估尼古丁的奖赏效应,有偏差的程序可能比无偏差的程序更合适。