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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity
Brain Research, Volume 959, No. 1, Year 2003
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Description
Nitric oxide (NO) is an unconventional transmitter molecule in the nervous system, synthesized by nitric oxide synthase (NOS) following activation of the N-methyl-D-aspartate (NMDA) receptor. Several in vivo studies have demonstrated that NO modulates the extracellular levels of various neurotransmitters in the central nervous system, while serotonin (5-HT) re-uptake may be influenced by the NO pathway. Moreover, inhibitors of NOS exhibit antidepressant-like and anxiolytic-like properties in various animal models. Therefore, the aims of the present study were to clarify the involvement of distinct antidepressants acting on the serotonin re-uptake site in the regulation of the activity of hippocampal NOS in vitro, in vivo and ex vivo. We found that citalopram, paroxetine, imipramine and NG-nitro-L-arginine dose dependently decreased the hippocampal NOS activity in vitro. Moreover, local administration of citalopram, paroxetine, tianeptine, imipramine and NG-nitro-L-arginine significantly decreased the hippocampal NOS activity in vivo at a concentration significantly lower than in vitro. No effect on NOS activity following retrodialysis with 5-HT was observed. Acute (5 mg/kg, s.c.) and chronic (3 weeks, 20 mg/kg/24 h) systemic administration of citalopram did not influence NOS activity ex vivo. The effects on NOS represent a response to structurally dissimilar serotonergic antidepressants. However, since these data reflect effects on basal NOS activity, we believe that serotonergic antidepressants do not directly affect NOS at dosages used clinically, but the findings may reflect a secondary action of antidepressants on the glutamate NMDA receptor following their primary inhibitory action at the 5-HT transporter. © 2002 Elsevier Science B.V. All rights reserved.
Authors & Co-Authors
Wegener, Gregers
Denmark, Aarhus
Aarhus Universitetshospital
Denmark, Aarhus
Aarhus Universitet
Volke, Vallo
Estonia, Tartu
Tartu Ülikool
Harvey, Brian H.
South Africa, Potchefstroom
North-west University
Rosenberg, Raben
Denmark, Aarhus
Aarhus Universitetshospital
Statistics
Citations: 160
Authors: 4
Affiliations: 4
Identifiers
Doi:
10.1016/S0006-8993(02)03738-1
ISSN:
00068993
Research Areas
Substance Abuse