Gören M Zafer, Küçükibrahimoglu Esra, Berkman Kemal, Terzioglu Berna
Department of Pharmacology and Clinical Pharmacology, School of Medicine, Marmara University, Haydarpasa, Istanbul 34668, Turkey.
Neurochem Res. 2007 Sep;32(9):1559-65. doi: 10.1007/s11064-007-9357-2. Epub 2007 May 8.
Fluoxetine, as a serotonin re-uptake inhibitor augments serotonin concentration within the synapse by inhibiting the serotonin transporter. The contribution of amino acids has also been shown in depression. We hypothesized that fluoxetine exerts its actions at least in part by intervening brain signaling operated by amino acid transmitters. Therefore the aim of this study is to supply neurochemical evidence that fluoxetine produces changes in amino acids in cerebrospinal fluid of rats. Sprague-Dawley rats were anesthetized and concentric microdialysis probes were implanted stereotaxically into the right lateral ventricle. Intraperitoneal fluoxetine (2.5 or 5 mg/kg) or physiological saline was administered and the probes were perfused with artificial cerebrospinal fluid at a rate of 1 mul/min. In the chronic fluoxetine group, the rats were treated daily with oral fluoxetine solution or inert syrup for 3 weeks. The microdialysis probes were placed on the 21st day and perfused the next day. Fluoxetine was ineffective in changing the cerebrospinal fluid GABA levels at the dose of 2.5 mg/kg but produced a significant increase in the perfusates following injection of 5 mg/kg of fluoxetine (P < 0.05). Oral fluoxetine administration (5 mg/kg) for 21 days also elevated the CSF GABA levels by approximately 2-fold (P < 0.05). L: -glutamic acid levels were not affected in all groups. These neurochemical findings show that fluoxetine, a selective serotonin re-uptake inhibitor affects brain GABA levels indirectly, and our results suggest that acute or chronic effects may be involved in beneficial and/or adverse effects of the drug.
氟西汀作为一种血清素再摄取抑制剂，通过抑制血清素转运体来提高突触内的血清素浓度。氨基酸在抑郁症中的作用也已得到证实。我们推测，氟西汀至少部分是通过干预由氨基酸递质介导的脑信号传导来发挥作用的。因此，本研究的目的是提供神经化学证据，证明氟西汀会使大鼠脑脊液中的氨基酸发生变化。将Sprague-Dawley大鼠麻醉后，通过立体定位将同心微透析探针植入右侧脑室。腹腔注射氟西汀（2.5或5mg/kg）或生理盐水，并以1微升/分钟的速率用人工脑脊液灌注探针。在慢性氟西汀组中，大鼠每天口服氟西汀溶液或惰性糖浆，持续3周。在第21天放置微透析探针，并于次日开始灌注。2.5mg/kg剂量的氟西汀对脑脊液γ-氨基丁酸（GABA）水平无影响，但注射5mg/kg氟西汀后，灌注液中的GABA水平显著升高（P<0.05）。口服氟西汀（5mg/kg）21天也使脑脊液GABA水平升高了约2倍（P<0.05）。所有组的L-谷氨酸水平均未受影响。这些神经化学研究结果表明，选择性血清素再摄取抑制剂氟西汀间接影响脑GABA水平，我们的结果表明，急性或慢性效应可能与该药物的有益和/或不良反应有关。
