Differential regulation of 5-hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats

Br J Pharmacol. 1996 Dec;119(7):1375-84. doi: 10.1111/j.1476-5381.1996.tb16049.x.

Abstract

1. Extracellular 5-hydroxytryptamine (5-HT) was determined in dorsal raphe nucleus (DRN), median raphe nucleus (MRN) and nucleus accumbens by use of microdialysis in unanaesthetized rats. 2. Infusion of the gamma-aminobutyric acid (GABA)A receptor agonist muscimol into DRN and MRN resulted in decreased 5-HT in DRN and MRN, respectively. Muscimol infusion into nucleus accumbens had no effect on 5-HT. 3. Infusion of the GABAA receptor antagonist bicuculline into DRN resulted in increased DRN and nucleus accumbens 5-HT. Bicuculline infusion into MRN had no effect on 5-HT. This suggests that endogenous GABA had a tonic, GABAA receptor-mediated inhibitory effect on 5-HT in DRN, but not in MRN. 4. Infusion of the GABAB receptor agonist baclofen into DRN produced a decrease in DRN 5-HT. Baclofen infusion into nucleus accumbens resulted in decreased nucleus accumbens 5-HT. This suggests that GABAB receptors are present in the area of cell bodies and terminals of 5-hydroxytryptaminergic neurones. 5. Infusion of the GABAB receptor antagonists phaclofen and 2-hydroxysaclofen had no effect on midbrain raphe and forebrain 5-HT. This suggests that GABAB receptors did not contribute to tonic inhibition of 5-HT release. 6. In conclusion, 5-HT release is physiologically regulated by distinct subtypes of GABA receptors in presynaptic and postsynaptic sites.

Publication types

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

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • Animals
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Ligands
  • Male
  • Microdialysis
  • Microinjections
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Prosencephalon / drug effects
  • Prosencephalon / metabolism*
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism*
  • Receptors, GABA-B / metabolism*
  • Serotonin / metabolism*
  • Serotonin Agents / pharmacology

Substances

  • GABA Agonists
  • GABA Antagonists
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Ligands
  • Receptors, GABA-A
  • Receptors, GABA-B
  • Serotonin Agents
  • 5,7-Dihydroxytryptamine
  • Serotonin