The effect of the selective 5-HT1A agonists alnespirone (S-20499) and 8-OH-DPAT on extracellular 5-hydroxytryptamine in different regions of rat brain
The effect of the selective 5-HT1A agonists alnespirone (S-20499) and 8-OH-DPAT on extracellular 5-hydroxytryptamine in different regions of rat brain
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DOI：
10.1038/sj.bjp.0701420
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发表时间：
1997-10-01
影响因子：
7.3
通讯作者：
Artigas, F
中科院分区：
文献类型：
--
作者：
Casanovas, JM;Lesourd, M;Artigas, F
1我们观察了选择性5-羟色胺受体激动剂阿尼螺酮(S-20499)全身给药对大鼠中缝背核、中缝正中核和四个前脑区(背侧纹状体、额叶皮质、腹侧海马区和背侧海马区)体内5-羟色胺释放的影响。在所研究的六个区域中，细胞外5-羟色胺呈剂量依赖性减少。在前脑，纹状体和额叶皮质的减少最大(最大分别减少到基线的23%和29%)。背侧和腹侧海马区的损伤程度较轻(约为基线的65%)。相反，中缝正中核引起的5-羟色胺的下降比中缝背核更明显(分别下降到基线的30%和60%)。选择性5-HT1a拮抗剂Way-100635(0.5mgkg(-1)，S.C.)拮抗阿尼螺酮(0.3 mg·kg~(-1)，S.C.)所致的5-羟色胺的降低。3 8-羟基-DPAT(0.025，0.1和0.3 mg kg(-1)，S.C.)局部选择性地降低细胞外5-羟色胺(例如，纹状体为基线的32%，背侧海马区为基线的69%)。在所研究的所有剂量下，8-OH-DPAT对中脑正中核中5-羟色胺的降低程度略高于中缝背核。两种化合物在接近各自ED50值的4个剂量(0.3 mg kg(-1)阿尼螺酮，0.025 mg kg(-1)8-OH-DPAT)对5-羟色胺的降低程度在所研究的所有区域中都是相同的。5这些数据表明，阿尼螺酮和8-OH-DPAT引起的5-羟色胺释放的减少在由中缝背核5-羟色胺能神经元支配的前脑区域更为重要。考虑到这两种5-HT1A激动剂在富含细胞体和神经末梢的区域的不同作用，这种区域选择性似乎不太可能由控制5-羟色胺释放的5H-T-1A自身受体的敏感性差异来解释。这提示5-HT1a受体对5-羟色胺的释放存在复杂的调控机制。
1 We have examined the effects of the systemic administration of the selective 5-HT1A agonist alnespirone (S-20499) on in vivo 5-hydroxytryptamine (5-HT) release in the dorsal raphe nucleus, the median raphe nucleus and four forebrain areas innervated differentially by both (dorsal striatum, frontal cortex, ventral hippocampus and dorsal hippocampus).2 Alnespirone (0.1-3 mg kg(-1), s.c.) dose-dependently reduced extracellular 5-HT in the six areas examined. In forebrain, the maximal reductions occurred in striatum and frontal cortex (maximal reduction to 23 and 29% of baseline, respectively). Those in dorsal and ventral hippocampus were more moderate (to ca 65% of baseline). In contrast, the decrease in 5-HT elicited in the median raphe nucleus was more marked than that in the dorsal raphe nucleus (to ca 30 and 60% of baseline, respectively). The selective 5-HT1A antagonist WAY-100635 (0.5 mg kg(-1), s.c.) prevented the decrease in 5-HT induced by alnespirone (0.3 mg kg(-1), s.c.) in frontal cortex.3 8-OH-DPAT (0.025, 0.1 and 0.3 mg kg(-1), s.c.) also reduced extracellular 5-HT in a regionally-selective manner (e.g., to 32% of baseline in striatum and to 69% in dorsal hippocampus at 0.1 mg kg(-1) s.c.). In midbrain, 8-OH-DPAT reduced the dialysate 5-HT slightly more in the median than in the dorsal raphe nucleus at all doses examined.4 Doses of both compounds close to their respective ED50 values (0.3 mg kg(-1) alnespirone, 0.025 mg kg(-1) 8-OH-DPAT) reduced 5-HT to a comparable extent in all regions examined. However, the reductions attained at higher doses were more pronounced for 8-OH-DPAT.5 These data show that the reduction of 5-HT release elicited by alnespirone and 8-OH-DPAT is more important in forebrain areas innervated by 5-hydroxytryptaminergic neurones of the dorsal raphe nucleus. This regional selectivity seems unlikely to be accounted for by differences in the sensitivity of 5H-T-1A autoreceptors controlling 5-HT release, given the dissimilar effects of these two 5-HT1A agonists in regions rich in cell bodies and nerve terminals. This suggests the presence of complex mechanisms of control of 5-HT release by 5-HT1A receptors.