Korkosz Agnieszka, Zatorski Pawel, Taracha Ewa, Plaznik Adam, Kostowski Wojciech, Bienkowski Przemyslaw
Department of Pharmacology, Institute of Psychiatry and Neurology, Sobieskiego 9 St., PL-02957 Warsaw, Poland.
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Sep 30;30(7):1283-90. doi: 10.1016/j.pnpbp.2006.04.024.
It has been shown that small doses of ethanol (<or= 1.0 g/kg) may antagonize the discriminative stimulus properties of nicotine. The aim of the present study was to evaluate whether ethanol could antagonize nicotine's rewarding effects in the conditioned place preference procedure. For comparison, effects of ethanol on nicotine-induced seizures were assessed. Male C57BL/6J mice were used in all experiments. Lower doses of nicotine (0.3 and 0.6 mg/kg, s.c.) induced significant conditioned place preference, while higher doses (0.9 and 1.2 mg/kg) induced neither conditioned place preference nor conditioned place aversion. In the following experiments, ethanol (0.5 or 1.0 g/kg, i.p.) was administered 5 min before 0.3 mg/kg nicotine. Ethanol did not antagonize nicotine-induced conditioned place preference. Contrary to our hypothesis, a non-significant (p = 0.07) enhancement of nicotine-induced place preference conditioning was observed in mice pre-treated with 1.0 g/kg ethanol. Both doses of ethanol (0.5 and 1.0 g/kg) suppressed seizures elicited by a high dose of nicotine (6.0 mg/kg). Ethanol totally eliminated clonic-tonic component of nicotine-induced seizures. Maximal blood ethanol levels after i.p. administration of 0.5 or 1.0 g/kg ethanol exceeded 60 and 115 mg%, respectively. The present results may indicate that the rewarding and seizure-inducing effects of nicotine are differentially modulated by clinically relevant concentrations of ethanol in mice.
已表明小剂量乙醇（≤1.0 g/kg）可能拮抗尼古丁的辨别刺激特性。本研究的目的是评估乙醇在条件性位置偏爱实验中是否能拮抗尼古丁的奖赏效应。为作比较，评估了乙醇对尼古丁诱发癫痫发作的影响。所有实验均使用雄性C57BL/6J小鼠。较低剂量的尼古丁（0.3和0.6 mg/kg，皮下注射）可诱导显著的条件性位置偏爱，而较高剂量（0.9和1.2 mg/kg）既不诱导条件性位置偏爱也不诱导条件性位置厌恶。在接下来的实验中，在注射0.3 mg/kg尼古丁前5分钟腹腔注射乙醇（0.5或1.0 g/kg）。乙醇并未拮抗尼古丁诱发的条件性位置偏爱。与我们的假设相反，在预先用1.0 g/kg乙醇处理的小鼠中，观察到尼古丁诱发的位置偏爱条件反射有不显著的增强（p = ０.07）。两种剂量的乙醇（0.5和1.0 g/kg）均抑制了高剂量尼古丁（6.0 mg/kg）诱发的癫痫发作。乙醇完全消除了尼古丁诱发癫痫发作的阵挛-强直成分。腹腔注射0.5或1.0 g/kg乙醇后的最大血乙醇水平分别超过60和115 mg%。目前的结果可能表明，在小鼠中，尼古丁的奖赏效应和诱发癫痫发作的效应受到临床相关浓度乙醇的不同调节。
