Differential regulation of 5-hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats.
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.
Tao
R
R
Department of Biological Sciences, Rutgers University, Piscataway, New Jersey 08855, USA.
Ma
Z
Z
Auerbach
S B
SB
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008024:Ligands; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008024:Ligands; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin