5-HT1B receptors modulate release of [3H]dopamine from rat striatal synaptosomes

The effect of the selective r5-HT1B agonist 3-(1,2,5,6-tetrahydro)-4-pyridil-5-pyrrolo [3,2-b] pyril-5-one (CP93,129) on the K+-evoked overflow of [3H]dopamine was studied in rat striatal synaptosomes loaded with [3H]dopamine. The aim of the study was to investigate the participation of 5-HT1B receptors in the serotonergic modulation of striatal dopaminergic transmission. The Ca2+-dependent, tetrodotoxin-resistant K+-evoked overflow of [3H]dopamine was inhibited by CP93,129 (0.01–100 µM) in a concentration-dependent manner (IC50=1.8 µM; maximal inhibition by 35.5% of control). [±]8-OH-DPAT, a 5-HT1A receptor agonist, [+/–]DOI, a 5-HT2 receptor agonist, and 2-methyl-5-hydroxytryptamine, a 5-HT3 receptor agonist, at concentrations ranging from 0.01 µM to 100 µM did not show any significant effect. Neither ketanserin (1 µM and 5 µM), a selective 5-HT2/5-HT1D receptor antagonist, nor ondansetron (1 µM), a 5-HT3 receptor antagonist, changed the inhibitory effect of CP93,129. SB224289, GR55562, GR127935, isamoltane and metergoline, selective and non-selective 5-HT1B receptor antagonists, in contrast, used at a concentration of 1 µM, antagonized the inhibitory effect of CP93,129 (3 µM and 10 µM). SB224289, a selective 5-HT1B receptor antagonist, inhibited the effect of CP93,129 in a concentration-dependent manner; the calculated Ki value was 1.8 nM. Our results indicate that in rat striatal axon terminals the K+-evoked release of dopamine is regulated by the presynaptic 5-HT1B heteroreceptors.