Irvine E E, Cheeta S, File S E
Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, SE1 1UL, London, UK.
Brain Res. 2001 Mar 9;894(1):95-100. doi: 10.1016/s0006-8993(01)01984-9.
The purpose of the present experiment was to explore the role of the dorsal hippocampus in mediating the development of tolerance to the anxiogenic effect of nicotine in the social interaction test of anxiety, and to determine whether tolerance develops to the effects of nicotine on [3H]-5-HT release in this area. Nicotine (1 microg) administered bilaterally into the dorsal hippocampus significantly reduced the time spent in social interaction in vehicle pre-treated rats, indicating an anxiogenic effect, but tolerance to this effect was seen in the rats pre-treated for 6 days with s.c. nicotine (0.1 mg/kg/day). In rats that had been pre-treated with vehicle for 6 days, nicotine (50-200 microM), significantly stimulated [3H]-5-HT release from dorsal hippocampal slices. This stimulation was significantly reduced in rats pre-treated with nicotine (0.1 mg/kg/day) for 6 days, indicating the development of tolerance to the effects of nicotine on 5-HT release. This suggests that tolerance to the anxiogenic effect of nicotine administered into the dorsal hippocampus could be mediated by a reduction in the nicotine enhancement of 5-HT release in this area.
本实验的目的是探讨背侧海马在介导焦虑社交互动测试中对尼古丁致焦虑作用产生耐受性过程中的作用，并确定在该区域尼古丁对[3H]-5-羟色胺（5-HT）释放的作用是否会产生耐受性。双侧向背侧海马注射尼古丁（1微克）可显著减少预先用溶剂处理的大鼠在社交互动中花费的时间，表明具有致焦虑作用，但在皮下注射尼古丁（0.1毫克/千克/天）预处理6天的大鼠中可观察到对该作用产生耐受性。在预先用溶剂处理6天的大鼠中，尼古丁（50 - 200微摩尔）可显著刺激背侧海马切片释放[3H]-5-HT。在预先用尼古丁（0.1毫克/千克/天）处理6天的大鼠中，这种刺激作用显著降低，表明对尼古丁对5-HT释放的作用产生了耐受性。这表明，对注射到背侧海马的尼古丁致焦虑作用产生的耐受性可能是由于该区域中尼古丁对5-HT释放增强作用的减弱所介导的。
