Serotonin-1B receptor-mediated inhibition of [3H]GABA release from rat ventral tegmental area slices

In order to assess a role of 5-HT(1B) receptors for regulation of GABA transmission in the ventral tegmental area (VTA), VTA slices from the rat were incubated with (3)H]GABA and beta-alanine, and superfused in the presence of nipecotic acid and aminooxyacetic acid. (3)H]GABA release was induced by exposures to the medium containing 30 mM potassium for 2 min. The results showed that high potassium-evoked (3)H]GABA release was sensitive to calcium withdrawal or blockade of sodium channels by tetrodotoxin, suggesting that tritium overflow induced by high potassium derived largely from neuronal stores. Administration of CP 93129 (0.15 and 0.45 microM), a 5-HT(1B) receptor agonist, or RU 24969 (0.15 and 0.45 microM), a 5-HT(1B/1A) receptor agonist, but not 8-OH-DPAT (0.45 microM), a 5-HT(1A) receptor agonist, inhibited high potassium-evoked (3)H]GABA release in a concentration-related manner. The RU 24969-induced inhibition of (3)H]GABA release was antagonized by either SB 216641, a 5-H(1B) receptor antagonist, or cyanopindolol, a 5-HT(1B/1A) receptor antagonist, but not by WAY 100635, a 5-HT(1A) receptor antagonist. Pre-treatment with SB 216641 also antagonized CP 93129-induced inhibition of (3)H]GABA release. The results support the hypothesis that 5-HT(1B) receptors within the VTA can function as heteroreceptors to inhibit GABA release.