Differential regulation of 5-hydroxytryptamine release by GABA(A) and GABA(B) 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 unanesthetized 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 nor effect on 5-HT. 3 Infusion of the GABA(A) receptor antgonist biscuculline 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, GABA(A) receptor-mediated inhibitory effect on 5-HT in DRN, but not in MRN. 4 Infusion of the GABA(B) 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 GABA(B) receptors are present in the area of cell bodies and terminals of 5-hydroxytryptaminergic neurones. 5 Infusion of the GABA(B) receptor antagonists phaclofen and 2-hydroxysaclofen had no effect on midbrain raphe and forebrain 5-HT. This suggest that GABA(B) 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.