Progressive attenuation of the firing activity of locus coeruleus noradrenergic neurons by sustained administration of selective serotonin reuptake inhibitors

The International Journal of Neuropsychopharmacology
S T SzaboP Blier

Abstract

Sustained administration of the selective serotonin (5-HT) reuptake inhibitors (SSRIs) citalopram for 2, 14, and 21 d, and paroxetine for 2 and 21 d (20 and 10 mg/kg.d, respectively, s.c. using osmotic minipumps) produced a gradual decrease in spontaneous firing activity of locus coeruleus (LC) noradrenergic neurons. In contrast, sustained desipramine administration for 2 and 21 d (10 mg/kg.d) robustly reduced LC firing activity, though only to the same extent, following these two treatment periods. The enhancement of the firing rate of LC neurons produced by the 5-HT1A agonist 8-OH-DPAT (10-50 &mgr;g/kg, i.v.) in desipramine- and citalopram-treated rats was abolished, indicating a desensitization of 5-HT1A receptors. However, the attenuation of the firing rate of LC neurons induced by the 5-HT2 agonist DOI (5-50 &mgr;g/kg, i.v.) was decreased approx. 2-fold in citalopram-treated rats but not significantly altered in desipramine-treated rats. Since 5-HT neurons exert a tonic inhibitory effect on LC neurons, it appears that enhancing 5-HT neurotransmission by sustained SSRI administration leads to a reduction of the firing rate of noradrenergic neurons. In conclusion, SSRIs attenuate the activity of noradrenergic neurons with a ...Continue Reading

Citations

Jun 19, 2004·Journal of Psychiatric Research·Jong-Min WooBum-Hee Yu
Nov 20, 2002·Biological Psychiatry·Justine M KentJack M Gorman
Feb 1, 2002·European Journal of Pharmacology·Maxime RicherPierre Blier
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Mar 1, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Olga ChernolozPierre Blier
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Jan 1, 2007·International Journal of Psychiatry in Clinical Practice·Pierre Blier, Mostafa El Mansari
Aug 25, 2012·Expert Opinion on Investigational Drugs·Gaël QuesseveurBruno P Guiard
Dec 14, 2011·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Ramez GhanbariPierre Blier
Apr 27, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Corina O BondiDavid A Morilak
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Apr 11, 2012·Behavioural Brain Research·J S de AndradeM B Viana

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