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[Homozygote mice deficient in serotonin 5-HT1B receptor and antidepressant effect of selective serotonin reuptake inhibitors]. 1998

A C Trillat, and I Malagié, and M Bourin, and C Jacquot, and R Hen, and A M Gardier
Laboratoire de Neuropharmacologie EAD MESR 98-213, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.

We use the knockout mice strategy to investigate the contribution of the 5-HT1B receptor in mediating the effects of selective serotonin reuptake inhibitors (SSRI). Using microdialysis in awake 129/Sv mice, we show that the absence of the 5-HT1B receptor in mutant mice (KO 1B -/-) potentiated the effect of paroxetine on extracellular 5-HT levels in the ventral hippocampus, but not in the frontal cortex compared to wild-type mice (WT). Furthermore, using the forced swimming test, we demonstrate that SSRIs decreased immobility of WT mice, and this effect is absent in KO 1B -/- mice showing therefore that activation of 5-HT1B receptors mediate the antidepressant-like effects of SSRIs. Taken together these findings suggest that 5-HT1B autoreceptors limit the effects of SSRI particularly in the hippocampus while postsynaptic 5-HT1B receptors are required for the antidepressant activity of SSRIs.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D005625 Frontal Lobe The part of the cerebral hemisphere anterior to the central sulcus, and anterior and superior to the lateral sulcus. Brodmann Area 8,Brodmann's Area 8,Frontal Cortex,Frontal Eye Fields,Lobus Frontalis,Supplementary Eye Field,Area 8, Brodmann,Area 8, Brodmann's,Brodmanns Area 8,Cortex, Frontal,Eye Field, Frontal,Eye Field, Supplementary,Eye Fields, Frontal,Frontal Cortices,Frontal Eye Field,Frontal Lobes,Lobe, Frontal,Supplementary Eye Fields
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D006720 Homozygote An individual in which both alleles at a given locus are identical. Homozygotes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000928 Antidepressive Agents Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems. Antidepressant,Antidepressant Drug,Antidepressant Medication,Antidepressants,Antidepressive Agent,Thymoanaleptic,Thymoanaleptics,Thymoleptic,Thymoleptics,Antidepressant Drugs,Agent, Antidepressive,Drug, Antidepressant,Medication, Antidepressant
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D017367 Selective Serotonin Reuptake Inhibitors Compounds that specifically inhibit the reuptake of serotonin in the brain. 5-HT Uptake Inhibitor,5-HT Uptake Inhibitors,5-Hydroxytryptamine Uptake Inhibitor,5-Hydroxytryptamine Uptake Inhibitors,SSRIs,Selective Serotonin Reuptake Inhibitor,Serotonin Reuptake Inhibitor,Serotonin Reuptake Inhibitors,Serotonin Uptake Inhibitor,Serotonin Uptake Inhibitors,Inhibitors, 5-HT Uptake,Inhibitors, 5-Hydroxytryptamine Uptake,Inhibitors, Serotonin Reuptake,Inhibitors, Serotonin Uptake,Reuptake Inhibitors, Serotonin,Uptake Inhibitors, 5-HT,Uptake Inhibitors, 5-Hydroxytryptamine,Uptake Inhibitors, Serotonin,Inhibitor, 5-HT Uptake,Inhibitor, 5-Hydroxytryptamine Uptake,Inhibitor, Serotonin Reuptake,Inhibitor, Serotonin Uptake,Reuptake Inhibitor, Serotonin,Uptake Inhibitor, 5-HT,Uptake Inhibitor, 5-Hydroxytryptamine,Uptake Inhibitor, Serotonin

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