Hasegawa Shu, Watanabe Arata, Nishi Kyoko, Nguyen Khanh Q, Diksic Mirko
Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, and Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Que., Canada H3A 2B4.
Neurochem Int. 2005 Feb;46(3):261-72. doi: 10.1016/j.neuint.2004.08.007. Epub 2004 Dec 31.
The effects of acute and chronic administration of the serotonin (5-HT)1B agonist CP-93,129, on 5-HT synthesis rates were evaluated using the alpha-[14C]methyl-L-tryptophan (alpha-MTrp) autoradiographic method. In the acute treatment study, CP-93,129 (7 mg/kg) was injected intraperitoneally 30 min before the alpha-MTrp injection (30 microCi over 2 min). A single dose of CP-93,129 caused a significant increase in the synthesis in the median raphe nucleus (MR) without a significant influence on the dorsal raphe nucleus (DR). There was a reduction in 5-HT synthesis in almost all of the projection areas. In the chronic treatment study, CP-93,129 was administered continuously (7 mg/kg/day) for 14 days using an osmotic minipump implanted subcutaneously. The chronic treatment with CP-93,129 did not produce a significant change in 5-HT synthesis in the raphe nuclei nor in the nerve terminal structures, except for the medial frontal bundle and the visual and sensory-motor cortices. The unaltered 5-HT synthesis rates in the chronic treatment study probably reflect a normalization of the synthesis as a result of the desensitization of 5-HT1B autoreceptors and/or heteroreceptors.
采用α-[14C]甲基-L-色氨酸（α-MTrp）放射自显影法评估了5-羟色胺（5-HT）1B激动剂CP-93,129急性和慢性给药对5-HT合成速率的影响。在急性治疗研究中，在注射α-MTrp（2分钟内注射30微居里）前30分钟腹腔注射CP-93,129（7毫克/千克）。单次剂量的CP-93,129使中缝正中核（MR）的合成显著增加，而对中缝背核（DR）无显著影响。几乎所有投射区域的5-HT合成均减少。在慢性治疗研究中，使用皮下植入的渗透微型泵连续给予CP-93,129（7毫克/千克/天），持续14天。除了内侧额束以及视觉和感觉运动皮层外，CP-93,129慢性治疗对中缝核以及神经终末结构中的5-HT合成未产生显著变化。慢性治疗研究中5-HT合成速率未改变可能反映了5-HT1B自身受体和/或异受体脱敏导致合成正常化。
