Reader T A, Ase A R, Le Marec N, Lalonde R
Centre de Recherche en Sciences Neurologiques, Département de physiologie, Faculté de médecine, Université de Montréal, H3C 3J7, Montreal, Québec, Canada.
Eur J Pharmacol. 2000 Jun 9;398(1):41-51. doi: 10.1016/s0014-2999(00)00298-3.
The effects of a chronic serotoninergic stimulation on brain monoamine levels and metabolism were studied in wild-type (+/+) mice and Lurcher (Lc/+) mutants. Endogenous serotonin, dopamine, noradrenaline and some of their major metabolites were measured in the frontal cortex, neostriatum, thalamus, brainstem, cerebellum and spinal cord. In +/+ mice, buspirone (1 mg/kg; i.p.) treatment during 40 days increased indoleamines, albeit with moderate changes in the ratios between tissue serotonin metabolites and endogenous serotonin, augmented noradrenaline contents in the spinal cord, and caused elevations of dopamine metabolites in most regions. In Lc/+ mutants, the effects of buspirone were attenuated, but higher L-tryptophan and indoleamine levels, suggest a storage of serotonin in a non-releasable compartment. In the hypoplastic Lc/+ cerebellum, indoleamine content was accrued, but with a decreased [serotonin metabolites]/[serotonin] ratio, indicating that the reorganized nerve terminals in Lc/+ mutants although they can synthesize and accumulate serotonin, may not utilize it efficiently in synaptic transmission.
在野生型（+/+）小鼠和Lurcher（Lc/+）突变体中研究了慢性5-羟色胺能刺激对脑单胺水平和代谢的影响。测定了额叶皮质、新纹状体、丘脑、脑干、小脑和脊髓中的内源性5-羟色胺、多巴胺、去甲肾上腺素及其一些主要代谢产物。在+/+小鼠中，40天期间给予丁螺环酮（1mg/kg；腹腔注射）治疗可增加吲哚胺，尽管组织5-羟色胺代谢产物与内源性5-羟色胺之间的比例变化适中，增加了脊髓中的去甲肾上腺素含量，并导致大多数区域的多巴胺代谢产物升高。在Lc/+突变体中，丁螺环酮的作用减弱，但较高的L-色氨酸和吲哚胺水平表明5-羟色胺储存在不可释放的隔室中。在发育不全的Lc/+小脑中，吲哚胺含量增加，但[5-羟色胺代谢产物]/[5-羟色胺]比值降低，这表明Lc/+突变体中重新组织的神经末梢虽然能够合成和积累5-羟色胺，但在突触传递中可能无法有效利用它。
