Abstract
5-Hydroxytryptamine (5-HT) release was measured by fast cyclic voltammetry in guinea-pig dorsal raphénucleus slices. Release was reproducibly evoked by a single 0.1 msec pulse of electrical stimulation. The 5-HT 1A receptor agonist 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH DPAT) produced a concentrationrelated inhibition of the stimulated 5-HT release, with 50% inhibition at 47 nM. This inhibition was competitively antagonized by N-tert- butyl 3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpropanamide dihydrochloride [(±)WAY100135], a selective 5-HT 1A receptor antagonist (pA 2 = 7.9). The 5-HT 1D receptor agonist sumatriptan also produced a concentration-related inhibition of 5-HT release, with 50% inhibition at 40 nM. The effect of suinatriptan on 5-HT release was antagonized by the 5-HT 1D receptor antagonist 2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1 yl) -phenyl]-amide (GR127935) (pA 2 = 8.7). Both (±)WAY100135 and GR127935 increased the 5-HT release evoked by a train of 5 pulses at 1 Hz, suggesting that they were antagonizing the feedback of endogenously released 5-HT onto its autoreceptors. These findings demonstrate for the first time the presence of functional 5-HT 1D as well as 5-HT 1A autoreceptors in the guinea-pig dorsal raphénucleus.
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