Biala Grazyna, Budzynska Barbara
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4 Staszica Street, 20-081 Lublin, Poland.
Eur J Pharmacol. 2006 May 10;537(1-3):85-93. doi: 10.1016/j.ejphar.2006.03.017. Epub 2006 Mar 20.
Reinstatement of drug-seeking behaviour in animals is relevant to drug relapse in humans. In the present study, we used the conditioned place preference paradigm to investigate the establishment, extinction, reinstatement and cross-reinstatement of nicotine-induced place conditioning in rats. Nicotine produced a place preference to the initially less-preferred compartment paired with its injections during conditioning (0.5 mg/kg, i.p., three drug sessions). Once established, nicotine place preference was extinguished by repeated training. Following this extinction phase, the reinstatement of place conditioning was investigated. For this purpose, nicotine-experienced rats were challenged with nicotine (0.5 mg/kg, i.p.) or morphine (10 mg/kg, i.p.). These priming injections of both drugs renewed a marked preference for the compartment previously paired with nicotine. In the second step, we examined the influence of the calcium channel antagonists, nimodipine (10 and 20 mg/kg, i.p.) and flunarizine (5 and 10 mg/kg, i.p.), on the reinstatement of nicotine-conditioned place preference induced by priming doses of nicotine and morphine. It was shown that the calcium channel blockers dose dependently attenuated the reinstatement of nicotine place preference induced by both drugs. These findings support the hypothesis that similar neural calcium-dependent mechanisms are involved in nicotine- and morphine-induced reinstatement. Finally, the conditioned place preference paradigm appears to be a useful tool for studies of the relapse of drug-seeking behaviour in laboratory animals.
动物中觅药行为的恢复与人类的药物复吸相关。在本研究中，我们使用条件性位置偏爱范式来研究大鼠中尼古丁诱导的位置条件反射的建立、消退、恢复和交叉恢复。在条件反射训练期间（0.5毫克/千克，腹腔注射，共三次给药），尼古丁与最初不太受偏爱的隔室配对注射，从而产生了对该隔室的位置偏爱。一旦建立，尼古丁位置偏爱通过重复训练而消退。在这个消退阶段之后，研究了位置条件反射的恢复。为此，让有尼古丁经历的大鼠接受尼古丁（0.5毫克/千克，腹腔注射）或吗啡（10毫克/千克，腹腔注射）的激发。这两种药物的这些激发注射重新引发了对先前与尼古丁配对的隔室的明显偏爱。在第二步中，我们研究了钙通道拮抗剂尼莫地平（10和20毫克/千克，腹腔注射）和氟桂利嗪（5和10毫克/千克，腹腔注射）对由尼古丁和吗啡的激发剂量诱导的尼古丁条件性位置偏爱的恢复的影响。结果表明，钙通道阻滞剂剂量依赖性地减弱了这两种药物诱导的尼古丁位置偏爱的恢复。这些发现支持了这样的假设，即相似的神经钙依赖性机制参与了尼古丁和吗啡诱导的恢复。最后，条件性位置偏爱范式似乎是研究实验动物中觅药行为复发的有用工具。
