Sustained administration of trazodone enhances serotonergic neurotransmission: in vivo electrophysiological study in the rat brain

The Journal of Pharmacology and Experimental Therapeutics
Ramez GhanbariP Blier

Abstract

Despite its clinical use for more than two decades, the mechanisms by which trazodone acts as an antidepressant are not clear, because it has affinity for a variety of 5-hydroxytryptamine (5-HT; serotonin) receptors and the 5-HT transporter. This study examined the effects of sustained trazodone administration on 5-HT neurotransmission. Electrophysiological recordings were conducted in anesthetized rats. Subcutaneously implanted minipumps delivered vehicle or trazodone (10 mg/kg/day) for 2 and 14 days. A 2-day trazodone administration suppressed the firing rate of raphe 5-HT neurons, which recovered to baseline after 14 days. This was attributable to 5-HT(1A) autoreceptor desensitization because the suppressant effect of the 5-HT autoreceptor agonist lysergic acid diethylamide was dampened in 14-day trazodone-treated rats. Prolonged trazodone administration did not change the sensitivity of postsynaptic 5-HT(1A) and α(2)-adrenergic receptors in hippocampus, but enhanced synaptic 5-HT levels because the 5-HT(1A) antagonist N-{2-[4 (2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) enhanced hippocampal firing in treated rats, but not in controls. Trazodone administration fo...Continue Reading

References

Dec 1, 1980·Journal of Neuroscience Methods·G PaxinosP C Emson
Jun 1, 1981·Life Sciences·M M Al-YassiriP K Bridges
Apr 1, 1994·Journal of Clinical Psychopharmacology·L A CunninghamE Hearst
Apr 16, 1998·European Journal of Pharmacology·M TatsumiE Richelson
Dec 14, 1999·European Journal of Pharmacology·M PazzagliG Pepeu
May 4, 2000·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·A BessonC de Montigny
Apr 3, 2001·The International Journal of Neuropsychopharmacology·C. Lindsay DeVaneRonald L. Miller
May 1, 1961·Journal of Neurophysiology·E R KANDEL, W A SPENCER
May 6, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Nasser HaddjeriPierre Blier
Mar 28, 2009·Journal of the American Academy of Child and Adolescent Psychiatry·Karen Dineen WagnerMario Saltarelli

❮ Previous
Next ❯

Citations

Feb 27, 2013·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Pierre Blier, Mostafa El Mansari
Dec 15, 2012·Pharmacological Reports : PR·Kinga K BorowiczStanisław J Czuczwar
Dec 14, 2011·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Ramez GhanbariPierre Blier
Oct 3, 2015·The International Journal of Neuropsychopharmacology·Chris A OosterhofPierre Blier
May 19, 2018·Human & Experimental Toxicology·O AtliS Ilgin
Jan 30, 2018·Frontiers in Pharmacology·Mariam B Camacho, Thomas J Anastasio
Sep 17, 2014·The Journal of Pharmacology and Experimental Therapeutics·Chris A OosterhofPierre Blier
Oct 21, 2017·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·D S Danilov
May 13, 2019·Experimental Brain Research·Paul J Fitzgerald, Brendon O Watson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.