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The characteristics of the spontaneous firing of serotoninergic neurons in the dorsal raphe nucleus and its control by serotonin (5‐hydroxytryptamine, 5‐HT) receptors were investigated in wild‐type and 5‐HT1B knock‐out (5‐HT1B–/–) mice of the 129/Sv strain, anaesthetized with chloral hydrate. In both groups of mice, 5‐HT neurons exhibited a regular activity with an identical firing rate of 0.5–4.5 spikes/s. Intravenous administration of the 5‐HT reuptake inhibitor citalopram or the 5‐HT1A agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) induced a dose‐dependent inhibition of 5‐HT neuronal firing which could be reversed by the selective 5‐HT1A antagonist N‐(2‐(4‐(2‐methoxyphenyl)‐1‐piperazinyl)ethyl)‐N‐(2‐pyridinyl)cyclohexane carboxamide (WAY 100635). Both strains were equally sensitive to 8‐OH‐DPAT (ED50 ∼ 6.3 μg/kg i.v.), but the mutants were less sensitive than wild‐type animals to citalopram (ED50 = 0.49 ± 0.02 and 0.28 ± 0.01 mg/kg i.v., respectively, P < 0.05). This difference could be reduced by pre‐treatment of wild‐type mice with the 5‐HT1B/1D antagonist 2′‐methyl‐4′‐(5‐methyl‐(1,2,4)oxadiazol‐3‐yl)‐biphenyl‐4‐carboxylic acid (4‐methoxy‐3‐(4‐methyl‐piperazine‐1‐yl)‐phenyl)amide (GR 127935), and might be accounted for by the lack of 5‐HT1B receptors and a higher density of 5‐HT reuptake sites (specifically labelled by (3H)citalopram) in 5‐HT1B–/– mice. In wild‐type but not 5‐HT1B–/– mice, the 5‐HT1B agonists 3‐(1,2,5,6‐tetrahydro‐4‐pyridyl)‐5‐propoxypyrrolo(3,2‐b)pyridine (CP 94253, 3 mg/kg i.v.) and 5‐methoxy‐3‐(1,2,3,6‐tetrahydropyridin‐4‐yl)‐1H‐indole (RU 24969, 0.6 mg/kg i.v.) increased the firing rate of 5‐HT neurons (+22.4 ± 2.8% and +13.7 ± 6.0%, respectively, P < 0.05), and this effect could be prevented by the 5‐HT1B antagonist GR 127935 (1 mg/kg i.v.). Altogether, these data indicate that in the mouse, the firing of 5‐HT neurons in the dorsal raphe nucleus is under both an inhibitory control through 5‐HT1A receptors and an excitatory influence through 5‐HT1B receptors.
European Journal of Neuroscience – Wiley
Published: Nov 1, 1999
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