TONIC INHIBITION OF STRIATAL DOPAMINE TRANSMISSION - EFFECTS OF BENZODIAZEPINE AND GABA-A RECEPTOR ANTAGONISTS ON EXTRACELLULAR DOPAMINE LEVELS

TONIC INHIBITION OF STRIATAL DOPAMINE TRANSMISSION - EFFECTS OF BENZODIAZEPINE AND GABA-A RECEPTOR ANTAGONISTS ON EXTRACELLULAR DOPAMINE LEVELS
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DOI:
10.1016/0006-8993(92)90851-y
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发表时间:
1992-12-18
期刊:
影响因子:
2.9
通讯作者:
MOGHADDAM, B
MOGHADDAM, B
中科院分区:
医学3区
文献类型:
--
作者:
GRUEN, RJ;FRIEDHOFF, AJ;MOGHADDAM, B

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目前,尚不清楚在苯二氮卓类/GABA受体复合物结合的配体是否发挥紧张性调节作用,纹状体多巴胺(DA)的传输。本研究采用在体微透析技术,观察苯二氮卓类(BZ)受体拮抗剂Ro 15 -1788和GABA(A)受体拮抗剂SR 95531对麻醉和清醒大鼠纹状体细胞外DA(DA[e])浓度的影响。Ro 15 -1788局部给药导致麻醉和清醒动物中DA[c]呈剂量依赖性增加。Ro 15 -1788诱导的DA[e]增加被BZ激动剂地西泮和GABA联合给药阻断。SR 95531局部给药还导致麻醉和清醒动物纹状体DA水平的剂量依赖性变化。SR 95531诱导的DA增加被GABA联合给药阻断。结果提示,GABA可能对纹状体DA的传递起紧张性抑制作用。
At present, it is unclear whether ligands which bind at the benzodiazepine/GABA receptor complex play a tonic modulatory role with regard to striatal dopamine (DA) transmission. The present study was designed to examine the effects of Ro15-1788, a benzodiazepine (BZ) receptor antagonist, and SR 95531, a GABA(A) receptor antagonist, on striatal extracellular DA (DA[e]) concentrations in anesthetized and awake rats using the technique of in vivo microdialysis. Local administration of Ro15-1788 resulted in a dose-dependent increase in DA[c] in both anesthetized and awake animals. The Ro15-1788-induced increase in DA[e] was blocked by coadministration of the BZ agonist diazepam, as well as GABA. Local administration of SR 95531 also resulted in a dose-dependent alteration in striatal DA levels in both anesthetized and awake animals. The SR 95531-induced increase in DA was blocked by coadministration of GABA. The results suggest that GABA may play a tonic inhibitory role with regard to striatal DA transmission.