Zetterström T, Fillenz M
University Laboratory of Physiology, Oxford, U.K.
Neuropharmacology. 1990 Feb;29(2):129-34. doi: 10.1016/0028-3908(90)90052-s.
The action of local administration of flurazepam on extracellular levels of dopamine (DA) and its metabolites 3,4 dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the anterior striatum and medial nucleus accumbens have been investigated using microdialysis. Flurazepam (10 microM), administered through the perfusion medium for 20 min, reduced levels of DA in dialysates from the nucleus accumbens by 60% while the same concentration of the drug had no effect on levels of DA in perfusates from the striatum. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (flumazenil) or with picrotoxin, a drug which blocks the GABAA receptor-associated chloride channel, inhibited the effect of flurazepam on levels of DA in the nucleus accumbens, which suggests that the effect was mediated by the multimolecular GABAA/benzodiazepine receptor complex. Administration of flurazepam had little effect on the two metabolites of DA, DOPAC and HVA, in either the nucleus accumbens or striatum. The inverse partial benzodiazepine agonist, FG 7142, had no significant action on the release of DA in the nucleus accumbens. These results suggest that the dopaminergic projection to the nucleus accumbens is more sensitive to benzodiazepine-induced inhibition than the projection to the striatum.
利用微透析技术研究了氟西泮局部给药对前纹状体和伏隔核内侧细胞外多巴胺（DA）水平及其代谢产物3,4 - 二羟基苯乙酸（DOPAC）和高香草酸（HVA）水平的影响。通过灌注介质给予氟西泮（10微摩尔）20分钟，伏隔核透析液中DA水平降低了60%，而相同浓度的该药物对纹状体灌注液中DA水平没有影响。用苯二氮䓬拮抗剂Ro 15 - 1788（氟马西尼）或用阻断GABAA受体相关氯离子通道的药物匹鲁卡品预处理，可抑制氟西泮对伏隔核中DA水平的影响，这表明该作用是由多分子GABAA/苯二氮䓬受体复合物介导的。给予氟西泮对伏隔核或纹状体中DA的两种代谢产物DOPAC和HVA几乎没有影响。反向部分苯二氮䓬激动剂FG 7142对伏隔核中DA的释放没有显著作用。这些结果表明，投射到伏隔核的多巴胺能神经比投射到纹状体的多巴胺能神经对苯二氮䓬诱导的抑制更敏感。
