Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
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Action Potentials / drug effects
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Adrenergic alpha-2 Receptor Agonists
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Adrenergic alpha-2 Receptor Antagonists
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Adrenergic alpha-Agonists / pharmacology
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Adrenergic alpha-Antagonists / pharmacology
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Amphetamines / pharmacology
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Brimonidine Tartrate
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Citalopram / pharmacology*
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Dose-Response Relationship, Drug
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Duloxetine Hydrochloride
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Idazoxan / pharmacology
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In Vitro Techniques
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Locus Coeruleus / cytology
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Locus Coeruleus / drug effects*
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Locus Coeruleus / physiology
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Male
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Methiothepin / pharmacology
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Naloxone / pharmacology
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Narcotic Antagonists / pharmacology
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Neurons / drug effects*
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Neurons / physiology
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Norepinephrine / pharmacology
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Oxazines / pharmacology
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Piperazines / pharmacology
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Piperidines / pharmacology
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Pyridines / pharmacology
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Quinoxalines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Adrenergic, alpha-2 / physiology*
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Receptors, Opioid, mu / antagonists & inhibitors
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Selective Serotonin Reuptake Inhibitors / pharmacology
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Serotonin / pharmacology
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Serotonin Antagonists / pharmacology
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Serotonin Receptor Agonists / pharmacology
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Thiophenes / pharmacology
Substances
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Adrenergic alpha-2 Receptor Agonists
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Adrenergic alpha-2 Receptor Antagonists
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Adrenergic alpha-Agonists
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Adrenergic alpha-Antagonists
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Amphetamines
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Bridged Bicyclo Compounds, Heterocyclic
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Narcotic Antagonists
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Oxazines
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Piperazines
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Piperidines
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Pyridines
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Quinoxalines
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Receptors, Adrenergic, alpha-2
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Receptors, Opioid, mu
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Serotonin Uptake Inhibitors
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Thiophenes
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Citalopram
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alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol
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Serotonin
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Naloxone
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Brimonidine Tartrate
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Methiothepin
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N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
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azasetron
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8-Hydroxy-2-(di-n-propylamino)tetralin
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Duloxetine Hydrochloride
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4-iodo-2,5-dimethoxyphenylisopropylamine
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Norepinephrine
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Idazoxan