Effects of cocaine, nicotine, dizocipline and alcohol on mice locomotor activity: cocaine-alcohol cross-sensitization involves upregulation of striatal dopamine transporter binding sites
Effects of cocaine, nicotine, dizocipline and alcohol on mice locomotor activity: cocaine-alcohol cross-sensitization involves upregulation of striatal dopamine transporter binding sites
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DOI：
10.1016/s0006-8993(98)01260-8
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发表时间：
1999-02-13
期刊：
影响因子：
2.9
通讯作者：
Martin, JL
中科院分区：
文献类型：
--
作者：
Itzhak, Y;Martin, JL
我们研究了可卡因、尼古丁、地佐环普林（MK-801）和酒精重复给药是否会导致这些药物之间的行为交叉致敏。Swiss韦伯斯特小鼠在其饲养笼中接受以下腹膜内（i. p.）连续5天注射：（a）盐水，（B）可卡因（20 mg/kg），（c）尼古丁（0.5 mg/kg），（d）MK-801（0.3 mg/kg）和（e）乙醇（2.0 g/kg）。10天停药期后，将每组（n = 30）分为3个亚组（n = 10），并接受可卡因、尼古丁或MK-801的激发注射。在自发活动笼（测试笼）中记录小鼠的水平和垂直运动。在检测的各种药物中，仅可卡因和乙醇经历小鼠对可卡因激发注射产生致敏反应; MK-801预处理小鼠仅对MK-801激发注射显示致敏反应。在第二个实验中，小鼠在其饲养笼中接受（a）盐水、（B）可卡因（20 mg/kg）或（c）乙醇（2.0 g/kg）5天，并在10天无药期后用腹膜内乙醇注射（2.0 g/kg）激发。可卡因和乙醇经验的小鼠与盐水经验的小鼠相比，对乙醇攻击产生显著的致敏作用。在用可卡因或乙醇重复治疗消失后11天，纹状体多巴胺转运蛋白（DAT）位点（通过[H-3]马吲哚结合）的密度评估显示DAT结合位点的数量显著增加（71-108%）。因此，在本研究中调查的各种精神兴奋剂中，仅观察到可卡因和乙醇之间的交叉致敏。我们测量的行为敏感性主要是“药物依赖性”，而不是“环境依赖性”，因为动物只暴露于测试笼一次。可卡因和乙醇诱导的行为敏化与纹状体DAT结合位点的上调相关，这一发现支持了类似的神经底物参与可卡因和酒精的精神兴奋/奖励效应的假设。(C)1999 Elsevier Science B. V.保留所有权利。
We investigated if repeated administration of cocaine, nicotine, dizocipline (MK-801) and alcohol yields behavioral cross-sensitization between these agents. Swiss Webster mice received in their home cage one of the following intraperitoneal (i.p.) injections for 5 consecutive days: (a) saline, (b) cocaine (20 mg/kg), (c) nicotine (0.5 mg/kg), (d) MK-801 (0.3 mg/kg) and (e) ethanol (2.0 g/kg). After a 10-day drug free period, each group (n = 30) was divided into three subgroups (n = 10) and received challenge injections of either cocaine, nicotine or MK-801. The horizontal and vertical movements of the mice were recorded in locomotor activity cages (test cage). Among the various drugs tested, only the cocaine and ethanol experienced mice developed sensitization to a challenge injection of cocaine; MK-801 pretreated mice showed a sensitized response only to a challenge injection of MK-801. In a second experiment, mice in their home cages received (a) saline, (b) cocaine (20 mg/kg) or (c) ethanol (2.0 g/kg) for 5 days, and challenged with an i.p. ethanol injection (2.0 g/kg) after a 10-day drug free period. Both, cocaine and ethanol experienced mice developed marked sensitization to ethanol challenge compared with the saline experienced mice. Assessment of the densities of striatal dopamine transporter (DAT) sites (by [H-3]mazindol binding) 11 days after the extinction of repeated treatment with either cocaine or ethanol revealed a significant increase (71-108%) in the number of DAT binding sites. Thus, among the various psychostimulants investigated in the present study cross-sensitization between cocaine and ethanol was only observed. The behavioral sensitization we measured was primarily 'drug-dependent', rather than 'context-dependent', because animals were exposed to the test cage only once. The finding that cocaine- and ethanol-induced behavioral sensitization is associated with upregulation of striatal DAT binding sites supports the hypothesis that similar neural substrates are involved in the psychomotor/rewarding effects of cocaine and alcohol. (C) 1999 Elsevier Science B.V. All rights reserved.