Lee E H
Life Sci. 1987 Feb 16;40(7):635-42. doi: 10.1016/0024-3205(87)90264-5.
Effects of apomorphine (APO) and clonidine (CLON) on the mesostriatal and mesolimbic serotonergic systems were examined in the present study. Both drugs selectively elevated serotonin (5-HT) concentrations in the dorsal raphe and the striatum without significantly altering 5-HT measures in the median raphe and the hippocampus. Apomorphine also increased tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) levels in the dorsal raphe and 5-HIAA level in the striatum. Clonidine did not markedly alter tryptophan and 5-HIAA measures, while it decreased 5-HT turnover rate in both region, as indicated by the ratio of 5-HIAA/5-HT levels. Co-administration of APO and CLON, at doses of each drug exerted maximum effects on 5-HT alone, produced an additive effect on 5-HT in the dorsal raphe, while their effects on 5-HT and 5-HIAA in the striatum were counteracting each other. Effects of APO on 5-HT and 5-HIAA were attributed to the elevation of 5-HT precursor tryptophan, while effects of CLON on 5-HT and 5-HIAA were due to a decreased rate of 5-HT turnover. Therefore, the present results support the hypothesis that the additive effects of APO and CLON on dorsal raphe 5-HT are mediated through different receptors and neuropharmacological mechanisms.
本研究考察了阿扑吗啡（APO）和可乐定（CLON）对中脑纹状体和中脑边缘5-羟色胺能系统的影响。两种药物均选择性地提高了背侧中缝核和纹状体中的5-羟色胺（5-HT）浓度，而对中缝正中核和海马体中的5-HT水平没有显著影响。阿扑吗啡还提高了背侧中缝核中的色氨酸和5-羟吲哚乙酸（5-HIAA）水平以及纹状体中的5-HIAA水平。可乐定没有明显改变色氨酸和5-HIAA的水平，但降低了这两个区域的5-HT周转率，5-HIAA/5-HT水平之比表明了这一点。单独使用时，APO和CLON的剂量对5-HT产生最大效应，联合给药时，它们对背侧中缝核中的5-HT产生相加效应，而它们对纹状体中5-HT和5-HIAA的效应相互抵消。APO对5-HT和5-HIAA的作用归因于5-HT前体色氨酸的升高，而CLON对5-HT和5-HIAA的作用则是由于5-HT周转率降低。因此，本研究结果支持以下假设：APO和CLON对背侧中缝核5-HT的相加效应是通过不同的受体和神经药理学机制介导的。
