Cadoni Cristina, Muto Tiziana, Di Chiara Gaetano
CNR Institute of Neuroscience, section of Cagliari, Cagliari, Italy.
Neuropharmacology. 2009 Oct-Nov;57(5-6):496-501. doi: 10.1016/j.neuropharm.2009.07.033. Epub 2009 Jul 30.
Genetic factors are known to affect the reinforcing properties of nicotine. Thus, inbred Lewis rats have been reported to be more sensitive to nicotine compared to Fischer 344 rats in self-administration, conditioned place preference and drug discrimination paradigms. In order to clarify the mechanisms of these differences we investigated, by means of dual probe microdialysis, the effect of different doses of nicotine (0.05, 0.1, 0.2, 0.4 mg/kg s.c.) on dopamine transmission in the shell and in the core of nucleus accumbens. Behavior was monitored during microdialysis. While no differences were observed between strains in dopamine basal values, Lewis rats, compared to Fischer 344 ones, showed in general a larger increase of DA transmission following nicotine both in the shell and in the core of the nucleus accumbens. In regard to behavioral stimulation no differences were observed between strains at higher doses while at the lowest doses Lewis rats appeared more sensitive than Fischer 344 rats to the locomotor stimulating effects of nicotine. These results suggest that strain-related differences in the sensitivity of mesolimbic dopamine transmission to nicotine might be involved in the reported differences in the reinforcing effect of nicotine in Lewis and Fischer 344 rats.
已知遗传因素会影响尼古丁的强化特性。因此，据报道，在自我给药、条件性位置偏爱和药物辨别范式中，近交系Lewis大鼠比Fischer 344大鼠对尼古丁更敏感。为了阐明这些差异的机制，我们通过双探针微透析研究了不同剂量的尼古丁（0.05、0.1、0.2、0.4mg/kg皮下注射）对伏隔核壳部和核心多巴胺传递的影响。在微透析过程中监测行为。虽然在多巴胺基础值方面未观察到品系间的差异，但与Fischer 344大鼠相比，Lewis大鼠总体上在尼古丁给药后伏隔核壳部和核心的多巴胺传递增加幅度更大。在行为刺激方面，在较高剂量时未观察到品系间的差异，而在最低剂量时，Lewis大鼠似乎比Fischer 344大鼠对尼古丁的运动刺激作用更敏感。这些结果表明，中脑边缘多巴胺传递对尼古丁敏感性的品系相关差异可能与Lewis大鼠和Fischer 344大鼠中报道的尼古丁强化作用差异有关。
