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

J Neurochem. 2004 May;89(4):886-96. doi: 10.1111/j.1471-4159.2004.02367.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Autoradiography
  • Binding, Competitive
  • Carrier Proteins / genetics*
  • Female
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacokinetics
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Male
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Nerve Tissue Proteins*
  • Neurons / drug effects
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Raphe Nuclei / metabolism
  • Receptor, Serotonin, 5-HT1A / deficiency
  • Receptor, Serotonin, 5-HT1A / genetics*
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptors, GABA-B / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Signal Transduction / physiology*

Substances

  • Carrier Proteins
  • GABA Agonists
  • GABA Antagonists
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, GABA-B
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • Receptor, Serotonin, 5-HT1A
  • Guanosine 5'-O-(3-Thiotriphosphate)