The selective serotonin reuptake inhibitor fluoxetine reduces striatal in vivo levels of voltammetric nitric oxide (NO): a feature of its antidepressant activity?
Voltammetric (electrochemical) methodologies such as differential pulse voltammetry and amperometry used together with electrically and chemically treated carbon fibre micro-electrodes (mCFE) allow selective monitoring of nitric oxide (NO). Preliminary in vitro studies have shown that the selective serotonin reuptake inhibitor (SSRI) antidepressant paroxetine inhibits constitutive nitric oxide synthase (cNOS) activity in animals and humans and that another SSRI such as fluoxetine reduced NO release in the media of synovial cells. The aim of this work was to verify by means of amperometry and specifically treated mCFE the capability of fluoxetine to alter the in vivo release of central NO, in the attempt to further clarify such putative antidepressant mechanism of action of this SSRI compound. The in vivo results support the chemical NO related nature of the endogenous amperometric signal evoked by NMDA injection in the striatum of anaesthetised rats, as pre-treatment with NOS inhibitor l-NAME prevented its appearance. Subsequently fluoxetine treatment resulted in decreased striatal NO, further supporting in vitro studies proposing a link between the serotonergic system and the NO system.
Crespi
Francesco
F
Biology, Neurosciences CEDD GlaxoSmithKline, Medicines Research Centre, Verona, Italy. Francesco.M.crespi@GSK.com
D000758:Anesthesia; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D055664:Electrochemical Techniques; D004567:Electrodes, Implanted; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D004791:Enzyme Inhibitors; D005473:Fluoxetine; D016202:N-Methylaspartate; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017367:Selective Serotonin Reuptake Inhibitors