Fung Y K, Lau Y S
University of Nebraska Medical Center, College of Dentistry, Department of Oral Biology, Lincoln 68583-0740.
Eur J Pharmacol. 1988 Aug 2;152(3):263-71. doi: 10.1016/0014-2999(88)90721-2.
Rats were pretreated with saline or nicotine (1.5 mg/kg per day) by subcutaneously implanting each animal with an Alzet osmotic mini-pump which continuously released saline or nicotine for 1, 5 and 14 days. At the end of each pretreatment period, animals were used for (i) determining their locomotor response to acutely injected nicotine (0.2 mg/kg, s.c.) and (ii) measuring the density of L-[3H]nicotine and [3H]spiperone binding sites in the striatum. We observed no changes in nicotine-induced locomotor response, striatal L-[3H]nicotine and [3H]spiperone binding in the animals pretreated with nicotine for 1 day. In rats which were pretreated with nicotine for 5 days, there was a significant increase in the nicotine-stimulated locomotor response which was associated with an increase in the number of L-[3H]nicotine binding sites and also with an elevated dopamine (DA) level in the striatum. The number of striatal [3H]spiperone binding sites was not affected. In animals pretreated with nicotine for 14 days, the nicotine-induced locomotor response remained to be potentiated. However, this response was correlated with an elevated number of striatal [3H]spiperone binding sites, whereas the number of striatal L-[3H]nicotine binding sites and the striatal DA level were normal. These results suggest that chronic nicotine-treated rats develop locomotor hyperactivity in response to nicotine initially due to increases of both the density of nicotinic receptors and DA concentration, followed by inducing DA receptor supersensitivity in the striatum.
通过给每只动物皮下植入一个Alzet渗透微型泵，持续释放生理盐水或尼古丁1天、5天和14天，对大鼠进行生理盐水或尼古丁（每天1.5毫克/千克）预处理。在每个预处理期结束时，将动物用于：（i）测定它们对急性注射尼古丁（0.2毫克/千克，皮下注射）的运动反应，以及（ii）测量纹状体中L-[3H]尼古丁和[3H]螺哌隆结合位点的密度。我们观察到，用尼古丁预处理1天的动物，尼古丁诱导的运动反应、纹状体L-[3H]尼古丁和[3H]螺哌隆结合没有变化。在用尼古丁预处理5天的大鼠中，尼古丁刺激的运动反应显著增加，这与L-[3H]尼古丁结合位点数量的增加以及纹状体中多巴胺（DA）水平的升高有关。纹状体[3H]螺哌隆结合位点的数量没有受到影响。在用尼古丁预处理14天的动物中，尼古丁诱导的运动反应仍然增强。然而，这种反应与纹状体[3H]螺哌隆结合位点数量的增加相关，而纹状体L-[3H]尼古丁结合位点的数量和纹状体DA水平正常。这些结果表明，长期用尼古丁处理的大鼠最初对尼古丁产生运动亢进，这是由于烟碱受体密度和DA浓度的增加，随后导致纹状体中DA受体超敏。
