5-HT sub(1A) and 5-HT sub(1B) receptors control the firing of serotoninergic neurons in the dorsal raphe nucleus of the mouse: studies in 5-HT sub(1B) knock-out mice

• Published in: The European journal of neuroscience Vol. 11; no. 11; pp. 3823 - 3831
• Main Authors: Evrard, A, Laporte, A M, Chastanet, M, Hen, R, Hamon, M, Adrien, J
• Format: Journal Article
• Language: English
• Published: 01.11.1999
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.1460-9568.1999.00800.x

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-HT sub(1B) knock-out (5-HT sub(1B)---) 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 0.5-4.5spikes-s. Intravenous administration of the 5-HT reuptake inhibitor citalopram or the 5-HT sub(1A) 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-HT sub(1A) 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 (ED sub(50) similar to 6.3 mu gkg i.v.), but the mutants were less sensitive than wild-type animals to citalopram (ED sub(50)=0.49 plus or minus 0.02 and 0.28 plus or minus 0.01mg-kg i.v., respectively, P<0.05). This difference could be reduced by pre-treatment of wild-type mice with the 5-HT sub(1B-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-HT sub(1B) receptors and a higher density of 5-HT reuptake sites (specifically labelled by [ super(3)H]citalopram) in 5-HT sub(1B)--- mice. In wild-type but not 5-HT sub(1B)--- mice, the 5-HT sub(1B) agonists 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]p yridine (CP 94253, 3mg-kg i.v.) and 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969, 0.6mg-kg i.v.) increased the firing rate of 5-HT neurons (+22.4 plus or minus 2.8% and +13.7 plus or minus 6.0%, respectively, P<0.05), and this effect could be prevented by the 5-HT sub(1B) antagonist GR 127935 (1mg-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-HT sub(1A) receptors and an excitatory influence through 5-HT sub(1B) receptors.