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 γ‐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 antgonist 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.