Inhibition of 5-hydroxytryptamine reuptake by the antidepressant citalopram in the locus coeruleus modulates the rat brain noradrenergic transmission in vivo

• Published in: Neuropharmacology Vol. 39; no. 11; pp. 2036 - 2043
• Main Authors: Mateo, Yolanda, Ruiz-Ortega, J.Angel, Pineda, Joseba, Ugedo, Luisa, Meana, J.Javier
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.2000; Elsevier
• Subjects: Animals; Antidepressants; Biological and medical sciences; citalopram; Citalopram - pharmacology; Locus coeruleus; Locus Coeruleus - drug effects; Locus Coeruleus - metabolism; Medical sciences; Microdialysis; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Noradrenaline; Norepinephrine - metabolism; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; selective serotonin reuptake inhibitors; Serotonin (5-HT); Serotonin - metabolism; Serotonin Uptake Inhibitors - pharmacology; Serotoninergic system; α 2-Adrenoceptors; Microdialysis; Antidepressants; Noradrenaline; Serotonin (5-HT); Locus coeruleus; α 2-Adrenoceptors; α2-Adrenergic receptor; Intraperitoneal administration; Rat; Serotonin; Psychotropic; Rodentia; Central nervous system; Catecholamine; Reuptake inhibitor; Citalopram; Dose activity relation; Vertebrata; Mammalia; Animal; Intracerebral administration; Antidepressant agent; Noradrenergic transmission; Norepinephrine; Antagonist; Mechanism of action; Brain (vertebrata)
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(00)00041-1

The in vivo effect of the serotonin (5-HT) reuptake inhibitor antidepressant citalopram, administered in the locus coeruleus (LC), on noradrenergic transmission was evaluated in the rat brain. In dual-probe microdialysis assays, citalopram (0.1–100 μM), in a concentration-dependent manner, increased extracellular noradrenaline (NA) in the LC and simultaneously decreased extracellular NA in the cingulate cortex (Cg). These effects of citalopram were abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (400 mg/kg, i.p.). When the α 2-adrenoceptor antagonist RS79948 (1 μM) was perfused in the LC, local citalopram increased NA dialysate in the LC but no longer modified NA dialysate in the Cg. In electrophysiological experiments, the administration of citalopram (100 μM) in the LC by reversal dialysis, decreased the firing rate of LC neurones. The results demonstrate in vivo that local administration of citalopram in the LC leads to a decreased release of NA in the Cg. This modulation seems to be the result of an increase in NA concentration in the LC and the subsequent inhibition of LC neurones via α 2-adrenoceptors. The effects of citalopram are dependent on the presence of endogenous 5-HT in the LC.