GABA(B) receptors in 5-HT transporter- and 5-HT1A receptor-knock-out mice: further evidence of a transduction pathway shared with 5-HT1A receptors.
The functional properties of GABA(B) receptors were examined in the dorsal raphe nucleus (DRN) and the hippocampus of knock-out mice devoid of the 5-HT transporter (5-HTT-/-) or the 5-HT(1A) receptor (5-HT(1A)-/-). Electrophysiological recordings in brain slices showed that the GABA(B) receptor agonist baclofen caused a lower hyperpolarization and neuronal firing inhibition of DRN 5-HT cells in 5-HTT-/- versus 5-HTT+/+ mice. In addition, [(35)S]GTP-gamma-S binding induced by GABA(B) receptor stimulation in the DRN was approximately 40% less in these mutants compared with wild-type mice. In contrast, GABA(B) receptors appeared functionally intact in the hippocampus of 5-HTT-/-, and in both this area and the DRN of 5-HT(1A)-knock-out mice. The unique functional changes of DRN GABA(B) receptors closely resembled those of 5-HT(1A) autoreceptors in 5-HTT-/- mice, further supporting the idea that both receptor types are coupled to a common pool of G-proteins in serotoninergic neurons.
Mannoury la Cour
Clotilde
C
INSERM U288, Neuropsychopharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Hanoun
Naïma
N
Melfort
Maxette
M
Hen
René
R
Lesch
Klaus-Peter
KP
Hamon
Michel
M
Lanfumey
Laurence
L
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018080:Receptors, GABA-B; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D044282:Receptor, Serotonin, 5-HT1A; D016244:Guanosine 5'-O-(3-Thiotriphosphate)