ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1460-9568.1999.00800.x
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