Pelloux Yann, Costentin Jean, Duterte-Boucher Dominique
Unité de Neuropsychopharmacologie Expérimentale, CNRS FRE 2735, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, IFRMP 23, Faculté de Médecine et de Pharmacie de Rouen, 22, Bld Gambetta, 76183 Rouen cedex, France.
Behav Brain Res. 2009 Feb 11;197(2):311-6. doi: 10.1016/j.bbr.2008.08.029. Epub 2008 Aug 29.
Some clinical studies have shown that anxiety disorders are often associated with drug dependence, although it remains unclear whether these disorders are primary or secondary to drug abuse. We have investigated whether anxiety may be a factor that predisposes to cocaine use. From an outbred Wistar strain, we have selected male rats regarded as anxious or non-anxious on the basis of their scores on two behavioural tests of unconditioned anxiety, the elevated plus-maze and the light/dark box test. They were also screened for their locomotor activity in an inescapable novel environment and for their preference for novelty presented in a free-choice. Rewarding effects of cocaine (2.5-20 mg/kg; i.p.) were then determined in the conditioned place preference paradigm (CPP). Anxious and non-anxious rats showed no difference in their responsiveness to inescapable novelty or their preference for novelty in a free-choice procedure. Only anxious rats developed a CPP induced by increasing doses of cocaine, the magnitude of CPP induced by the 10 mg/kg dose of cocaine being significantly higher than that observed in anxious rats conditioned with saline. These results suggest that anxiety affects the sensitivity to aversive/anxiogenic effects of cocaine. Thus, anxious rats which were highly responsive to positive effects of cocaine may be more prone to develop cocaine addiction than non-anxious rats.
一些临床研究表明,焦虑症常与药物依赖相关,尽管这些疾病是药物滥用的原发性还是继发性尚不清楚。我们研究了焦虑是否可能是易导致可卡因使用的一个因素。从远交Wistar品系中,我们根据大鼠在两项非条件性焦虑行为测试(高架十字迷宫和明暗箱测试)中的得分,挑选出被视为焦虑或非焦虑的雄性大鼠。还在一个无法逃避的新环境中对它们的运动活动进行了筛选,并在自由选择中对它们对新奇事物的偏好进行了筛选。然后在条件性位置偏爱范式(CPP)中测定可卡因(2.5 - 20毫克/千克;腹腔注射)的奖赏效应。焦虑和非焦虑大鼠在对无法逃避的新奇事物的反应性或自由选择程序中对新奇事物的偏好方面没有差异。只有焦虑大鼠在可卡因剂量增加时产生了CPP,10毫克/千克剂量的可卡因诱导的CPP程度显著高于用生理盐水处理的焦虑大鼠。这些结果表明,焦虑会影响对可卡因厌恶/致焦虑作用的敏感性。因此,对可卡因积极作用反应强烈的焦虑大鼠可能比非焦虑大鼠更容易形成可卡因成瘾。