Bosker F J, Klompmakers A A, Westenberg H G
Rudolf Magnus Institute for Neurosciences, Department of Psychiatry, Utrecht University, The Netherlands.
Neuropharmacology. 1995 May;34(5):501-8. doi: 10.1016/0028-3908(95)00023-y.
The delay in clinical effects of selective serotonin reuptake inhibitors (SSRIs) suggest the existence of adaptive phenomena, such as receptor sensitivity changes. To examine the effects of repeated administration of SSRIs on serotonin neurotransmission, we investigated the effects of acute and chronic administration of the SSRI fluvoxamine on the extracellular levels of 5-HT in the median raphe nucleus and dorsal hippocampus of conscious rats by means of brain microdialysis. A single oral dose of fluvoxamine (30 mg/kg) augmented extracellular 5-HT in the median raphe and dorsal hippocampus to 270 and 191% of baseline level, respectively. Administration of fluvoxamine (30 mg/kg) or vehicle for 14 days did not affect 5-HT baseline levels. Moreover, the increase in extracellular 5-HT in the median raphe nucleus and dorsal hippocampus after an oral dose of fluvoxamine (30 mg/kg) in rats chronically treated with fluvoxamine was not different from rats treated with vehicle. Using RU 24969 as a probe for the sensitivity of the 5-HT1B autoreceptors in the dorsal hippocampus, no change in receptor sensitivity could be observed. These results demonstrate that repeated oral treatment with fluvoxamine does not affect extracellular 5-HT in the median raphe and dorsal hippocampus, suggesting that presynaptic functional changes of 5-HT in the brain areas tested are not implicated in the observed delayed onset of action of this SSRI in humans.
选择性5-羟色胺再摄取抑制剂（SSRIs）临床疗效出现延迟，提示存在适应性现象，如受体敏感性变化。为研究重复给予SSRIs对5-羟色胺神经传递的影响，我们采用脑微透析法，研究了SSRI氟伏沙明急性和慢性给药对清醒大鼠中缝背核和背侧海马中5-羟色胺细胞外水平的影响。单次口服氟伏沙明（30毫克/千克）可使中缝背核和背侧海马中的细胞外5-羟色胺分别增加至基线水平的270%和191%。给予氟伏沙明（30毫克/千克）或赋形剂14天不影响5-羟色胺基线水平。此外，长期接受氟伏沙明治疗的大鼠口服一剂氟伏沙明（30毫克/千克）后，中缝背核和背侧海马中细胞外5-羟色胺的增加与接受赋形剂治疗的大鼠无差异。使用RU 24969作为背侧海马中5-HT1B自身受体敏感性的探针，未观察到受体敏感性变化。这些结果表明，重复口服氟伏沙明不影响中缝背核和背侧海马中的细胞外5-羟色胺，提示在所测试脑区中5-羟色胺的突触前功能变化与该SSRI在人类中观察到的延迟起效无关。
