Selective serotonin reuptake inhibitors enhance cocaine-induced locomotor activity and dopamine release in the nucleus accumbens
Selective serotonin reuptake inhibitors enhance cocaine-induced locomotor activity and dopamine release in the nucleus accumbens
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DOI：
10.1016/s0028-3908(02)00381-7
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发表时间：
2003-03-01
影响因子：
4.7
通讯作者：
Cunningham, KA
中科院分区：
文献类型：
--
作者：
Bubar, MJ;McMahon, LR;Cunningham, KA
5-羟色胺（5-HT）在介导可卡因行为效应中的作用可能部分与5-HT调节多巴胺（DA）中伏隔神经通路功能的能力有关。在本研究中，分析了选择性5-羟色胺再摄取抑制剂（SSRI）氟西汀（10 mg/kg，IP）和氟伏沙明（10和20 mg/kg，IP）改变可卡因（10 mg/kg，IP）诱导的活动过度和中脑核（NAc）中DA释放的能力。氟西汀或氟伏沙明的全身给药以剂量依赖性方式增强可卡因诱导的自发活动;氟西汀（10 mg/kg，IP）也增强了NAc中可卡因（10 mg/kg，IP）诱导的DA外排。为了检验NAc作为全身性给予可卡因后这些作用的基础的作用位点的假设，在全身性给予可卡因（10 mg/kg，IP）之前，将氟西汀（1和3 μ g/0.2穆尔/侧）或氟伏沙明（1和3 μ g/0.2穆尔/侧）微输注到NAc壳中。NAc壳内输注3 μ g氟西汀或氟伏沙明增强可卡因诱导的多动，而通过植入NAc壳的微透析探针输注氟西汀（1 μ M）增强可卡因（10 mg/kg，IP）诱导的DA流出NAc。因此，SSRIs全身注射增强可卡因诱发的NAc活动过度和DA流出的能力部分是由SSRIs在NAc中的局部作用介导的。(C)2003爱思唯尔科技有限公司版权所有。
The role for serotonin (5-HT) in mediating the behavioral effects of cocaine may be related in part to the ability of 5-HT to modulate the function of the dopan-tine (DA) mesoaccumbens pathways. In the present study, the ability of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine (10 mg/kg, IP) and fluvoxamine (10 and 20 mg/kg, IP) to alter cocaine (10 mg/kg, IP)induced hyperactivity and DA release in the nucleus accumbens (NAc) was analyzed in male Sprague-Dawley rats. Systemic administration of either fluoxetine or fluvoxamine enhanced cocaine-induced locomotor activity in a dose-dependent manner; fluoxetine (10 mg/kg, IP) also enhanced cocaine (10 mg/kg, IP)-induced DA efflux in the NAc. To test the hypothesis that the NAc serves as the locus of action underlying these effects following systemic cocaine administration, fluoxetine (1 and 3 mug/0.2 mul/side) or fluvoxamine (1 and 3 mug/0.2 mul/side) was microinfused into the NAc shell prior to systemic administration of cocaine (10 mg/kg, IP). Intra-NAc shell infusion of 3 mug of fluoxetine or fluvoxamine enhanced cocaine-induced hyperactivity, while infusion of fluoxetine (1 muM) through the microdialysis probe implanted into the NAc shell enhanced cocaine (10 mg/kg, IP)-induced DA efflux in the NAc. Thus, the ability of systemic injection of SSRIs to enhance cocaine-evoked hyperactivity and DA efflux in the NAc is mediated in part by local actions of the SSRIs in the NAc. (C) 2003 Elsevier Science Ltd. All rights reserved.