Invernizzi R, Bramante M, Samanin R
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Brain Res. 1995 Oct 23;696(1-2):62-6. doi: 10.1016/0006-8993(95)00730-e.
Citalopram, 1 and 10 mg/kg i.p., that in a previous study using identical treatment and dialysis conditions had little or no effect on dialysate serotonin (5-HT) in the frontal cortex, dose-dependently raised the extracellular concentrations of 5-HT in the dorsal hippocampus, by 70% and 205% respectively at the peak. In animals given 10 mg/kg citalopram twice daily for 14 days, intraperitoneal doses of 1 and 10 mg/kg or infusion of 10(-8) - 10(-6) M through the hippocampal probe raised dialysate 5-HT in the dorsal hippocampus similarly in animals treated chronically with citalopram or saline. A dose of 100 micrograms/kg 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), an agonist at 5-HT1A receptors, reduced hippocampal extracellular 5-HT concentrations to the same extent in rats repeatedly given saline or citalopram. Half this dose had no such effect in either group. The effect of citalopram and the sensitivity of autoreceptors controlling 5-HT release in the dorsal hippocampus were unaffected by a chronic treatment known to facilitate the drug's effect on dialysate 5-HT and to reduce the sensitivity of 5-HT1A receptors controlling 5-HT release in the frontal cortex. The effects of acute and chronic treatment with citalopram on dialysate 5-HT in the rat brain thus appear to differ in at least two brain regions: the frontal cortex and the dorsal hippocampus.
西酞普兰腹腔注射剂量为1和10mg/kg，在之前一项采用相同治疗和透析条件的研究中，该剂量对额叶皮质透析液中的5-羟色胺（5-HT）几乎没有影响或无影响，但能剂量依赖性地提高背侧海马体中5-HT的细胞外浓度，峰值时分别提高70%和205%。在每天两次给予10mg/kg西酞普兰、连续给药14天的动物中，腹腔注射1和10mg/kg剂量或通过海马探针输注10(-8)-10(-6)M的药物，在长期接受西酞普兰或生理盐水治疗的动物中，背侧海马体中的透析液5-HT升高情况相似。5-HT1A受体激动剂8-羟基-2-(二正丙基氨基)四氢萘（8-OH-DPAT）剂量为100μg/kg时，在反复给予生理盐水或西酞普兰的大鼠中，可使海马体细胞外5-HT浓度降低相同程度。该剂量减半时，两组均无此效应。已知一种慢性治疗可增强药物对透析液5-HT的作用，并降低控制额叶皮质中5-HT释放的5-HT1A受体的敏感性，但这种慢性治疗并不影响西酞普兰的作用以及控制背侧海马体中5-HT释放的自身受体的敏感性。因此，西酞普兰急性和慢性治疗对大鼠脑内透析液5-HT的影响在至少两个脑区存在差异：额叶皮质和背侧海马体。
