alpha(2)-Adrenoceptor involvement in the in vitro inhibitory effect of citalopram on a subpopulation of rat locus coeruleus neurons.
The aim of the present study was to investigate the modulation of locus coeruleus neurons by the selective serotonin (5-HT) reuptake inhibitor citalopram using single-unit extracellular recordings in rat brain slices. Citalopram inhibited the activity of a subpopulation of locus coeruleus neurons; thus 10 microM citalopram inhibited neurons by 53+/-17% (5 out of 15 cells), whereas the inhibition due to 100 microM was 64+/-4% (32 out of 42 cells). This effect was partially reversed (47+/-11%) by the alpha(2)-adrenoceptor antagonist idazoxan (10 microM), whereas it was unaffected by antagonists for 5-HT(1A), 5-HT(2,) and 5-HT(3) receptors, and mu opioid receptors. 5-HT (50 or 200 microM), the 5-HT(1A) receptor agonist 8-OH-DPAT (+/-)-8-hydroxy-2-(DI-n-propyl-amino) tetralin hydrobromide, 10 microM) and the 5-HT(2) receptor agonist DOI ([+/-]-2,5-dimetoxy-4-iodoamphetamine) hydrochloride, 10 or 30 microM) also inhibited a subpopulation of locus coeruleus cells. In addition, citalopram but not 5-HT, enhanced by 1.7 fold the inhibitory effect of noradrenaline. Long-term treatment with citalopram (20 mg/kg/day) did not modify the effect of noradrenaline and bromoxidine. Taken together, our results indicate that citalopram exerts an inhibitory effect on locus coeruleus noradrenergic neurons. alpha(2)-adrenoceptor activation may underlie this effect as a result of elevated levels of noradrenaline in the synaptic cleft.
Departamento de Farmacología, Universidad del País Vasco, E-48940 Leioa, Vizcaya, Spain.
Laura
L
Grandoso
María
M
Torrecilla
Joseba
J
Pineda
Luisa
L
Ugedo
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D019329:Idazoxan / Q000494:pharmacology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000662:Amphetamines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000068438:Brimonidine Tartrate; D015283:Citalopram; D000068736:Duloxetine Hydrochloride; D019329:Idazoxan; D008719:Methiothepin; D009270:Naloxone; D009292:Narcotic Antagonists; D009638:Norepinephrine; D010078:Oxazines; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D017450:Receptors, Opioid, mu; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C070671:azasetron; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine