Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat
Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat
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DOI：
10.1002/syn.10238
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发表时间：
2003-10-01
期刊：
影响因子：
2.3
通讯作者：
Fratta, W
中科院分区：
文献类型：
--
作者：
Fadda, P;Scherma, M;Fratta, W
最近提供的证据表明，GABA 能系统通过对中脑边缘多巴胺能神经元的作用，具体参与调节几种滥用药物的正强化特性。 GABA(B) 受体激动剂巴氯芬已被提议作为一种潜在的治疗剂，用于临床治疗多种形式的药物成瘾。在本研究中，使用体内微透析技术，我们研究了巴氯芬对尼古丁、可卡因和吗啡诱导的伏隔核壳中细胞外多巴胺 (DA) 水平增加的影响，伏隔核是自由活动大鼠的大脑区域，据称参与调节几种滥用药物的中枢作用。正如预期的那样，给大鼠注射尼古丁（0.6 mg/kg s.c.）、吗啡（5 mg/kg s.c.）和可卡因（7.5 mg/kg i.p.）可诱导伏隔核中细胞外 DA 浓度显着增加，达到最大值 +205 +/- 8.4%、+300 +/- 22.2% 和 +370 +/- 30.7%。分别。巴氯芬（1.25 和 2.5 mg/kg 腹腔注射）预处理可剂量依赖性地减少伏隔核壳中尼古丁、吗啡和可卡因诱发的 DA 释放。此外，单独使用巴氯芬在 180 分钟内不会引起基础 DA 细胞外水平的变化。综上所述，我们的数据与之前的报告一致，证明巴氯芬调节中脑边缘 DAergic 传递的能力，并表明巴氯芬是多种药物滥用药物治疗的假定候选药物。 (C) 2003 Wiley-Liss, Inc.
Evidence recently provided has suggested a specific involvement of the GABAergic system in modulating positive reinforcing properties of several drugs of abuse through an action on mesolimbic dopaminergic neurons. The GABA(B) receptor agonist baclofen has been proposed as a potential therapeutic agent for the clinical treatment of several forms of drug addiction. In the present study, using the in vivo microdialysis technique, we investigated the effect of baclofen on nicotine, cocaine, and morphine-induced increase in extracellular dopamine (DA) levels in the shell of the nucleus accumbens, a brain area supposedly involved in the modulation of the central effects of several drugs of abuse, of freely moving rats. As expected, nicotine (0.6 mg/kg s.c.), morphine (5 mg/kg s.c.), and cocaine (7.5 mg/kg i.p.) administration in rats induced a marked increase in extracellular DA concentrations in the nucleus accumbens, reaching a maximum value of +205 +/- 8.4%, +300 +/- 22.2%, and +370 +/- 30.7%, respectively. Pretreatment with baclofen (1.25 and 2.5 mg/kg i.p.) dose-dependently reduced the nicotine-, morphine-, and cocaine-evoked DA release in the shell of the nucleus accumbens. Furthermore, baclofen alone did not elicit changes in basal DA extracellular levels up to 180 min. Taken together, our data are in line with previous reports demonstrating the ability of baclofen to modulate the mesolimbic DAergic transmission and indicate baclofen as a putative candidate in the pharmacotherapy of polydrug abuse. (C) 2003 Wiley-Liss, Inc.