Local, but not systemic, administration of serotonergic antidepressants
decreases hippocampal nitric oxide synthase activity
Wegener G, Volke V, Harvey BH, Rosenberg R.
Institute for Basic Psychiatric Research,
Department of Biological Psychiatry,
Skovagervej 2, DK-8240 Risskov, Denmark.
Brain Res. 2003 Jan 3;959(1):128-34.
ABSTRACTNitric 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 N(G)-nitro-L-arginine dose dependently decreased the hippocampal NOS activity in vitro. Moreover, local administration of citalopram, paroxetine, tianeptine, imipramine and N(G)-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.Fear
Stress, memory and depression
Tianeptine for anxious depressives
Electrophysiological effects of tianeptine
Tianeptine (Stablon) v paroxetine (Paxil, Seroxat)
Structure-activity relationships/tricyclic antidepressants
and further reading
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family