Dual control of dorsal raphe serotonergic neurons by GABA(B) receptors. Electrophysiological and microdialysis studies

Synapse. 2000 Apr;36(1):21-34. doi: 10.1002/(SICI)1098-2396(200004)36:1<21::AID-SYN3>3.0.CO;2-D.

Abstract

We assessed the role of GABA(B) receptors in the control of serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN) by using microdialysis in vivo and intra- and extracellular recording in vitro in the rat. The GABA(B) agonist R(+)baclofen (but not the inactive S(-)enantiomer) enhanced the 5-HT output in the DRN (4. 7-fold at 15 mg/kg s.c.) and, to a much lesser extent, striatum of unanesthetized rats. Phaclofen (2 mg/kg s.c.) antagonized the effects of 6 mg/kg R(+)baclofen in dorsal striatum. Using dual-probe microdialysis, R(+)baclofen (0.1-100 microM) applied in the DRN enhanced the local 5-HT output (4.5-fold at 100 microM) but decreased that in striatum at 100 microM. At concentrations higher than 100 microM there was a moderate decrement in the elevation of 5-HT in the DRN. In midbrain slices, bath R(+)baclofen exerted a biphasic effect on DRN 5-HT neurons. Consistent with a reduced striatal 5-HT release when infused in the DRN, R(+)baclofen (0.1-30 microM) induced an outward current in 5-HT neurons (IC(50) = 1.4 microM). Lower R(+)baclofen concentrations (0.01-1 microM) preferentially reduced GABAergic inhibitory postsynaptic currents induced by N-methyl-D-aspartate (20 microM) in 5-HT neurons (IC(50) = 72 nM). Using extracellular recordings, R(+)baclofen (300 nM) enhanced the ability of NMDA to induce firing in a subpopulation of serotonergic neurons. These results are consistent with a preferential activation by a low concentration of R(+)baclofen of presynaptic GABA(B) receptors on GABAergic afferents that could disinhibit 5-HT neurons and increase 5-HT release.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Electrophysiology
  • Extracellular Space / physiology
  • GABA Agonists / pharmacology
  • GABA-B Receptor Agonists
  • In Vitro Techniques
  • Male
  • Microdialysis
  • Microelectrodes
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Raphe Nuclei / cytology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-B / physiology*
  • Serotonin / physiology*
  • gamma-Aminobutyric Acid / physiology

Substances

  • GABA Agonists
  • GABA-B Receptor Agonists
  • Receptors, GABA-B
  • Serotonin
  • gamma-Aminobutyric Acid
  • Baclofen