Congestri Francesco, Formenti Francesca, Sonntag Viviana, Hdou Gael, Crespi Francesco
Biology Dept, GlaxoSmithKline, Medicines Research Centre, Verona, Italy.
Sensors (Basel). 2008 Nov 4;8(11):6936-6951. doi: 10.3390/s8116936.
Dopamine (DA) D3 receptors have been associated with drug intake and abuse and selectively distribute in the brain circuits responding to drug administration. Here we examined the effects of an acute systemic administration of cocaine (15 mg/kg) alone or preceded by treatment with the selective D3 receptor antagonist SB-277011-A (10 mg/kg) on DA levels concurrently in the rat nucleus accumbens shell and core sub-regions (NAcshell and NAccore, respectively). It is shown that cocaine increases extracellular DA in both compartments and that blocking D3 receptors with SB-277011-A, although the latter is devoid of dopaminergic effects per se, potentiates these effects. No differences in the amplitude of the response were observed between NAcshell and NAccore compartments, though the dopaminergic response in the NAcshell was transient whereas that in the NAccore rose slowly to reach a plateau. These results demonstrate the feasibility to use multiprobe voltammetry to measure discrete monoaminergic responses in discrete areas of the brain and confirm the effect of D3 receptors antagonist at modifying the neurochemical effects of cocaine.
多巴胺(DA)D3受体与药物摄入及滥用相关,并选择性地分布于对药物给药产生反应的脑回路中。在此,我们研究了单独急性全身给予可卡因(15毫克/千克),或在给予可卡因之前先用选择性D3受体拮抗剂SB - 277011 - A(10毫克/千克)处理,对大鼠伏隔核壳和核心子区域(分别为NAc壳和NAc核心)中多巴胺水平的同时影响。结果表明,可卡因会增加两个区室中的细胞外多巴胺水平,并且用SB - 277011 - A阻断D3受体,尽管后者本身没有多巴胺能效应,但会增强这些效应。在NAc壳和NAc核心区室之间未观察到反应幅度的差异,不过NAc壳中的多巴胺能反应是短暂的,而NAc核心中的反应则缓慢上升至平台期。这些结果证明了使用多探头伏安法测量大脑离散区域中离散单胺能反应的可行性,并证实了D3受体拮抗剂在改变可卡因神经化学效应方面的作用。