K+-evoked [3H]-5-HT release from rat frontal cortex slices: the effect of 5-HT agonists and antagonists

The pharmacological characteristics of a pre-junctional 5-HT autoreceptor have been studied by following the Ca²⁺-dependent, K⁺-evoked release of ³H]-5-HT from preloaded rat frontal cortex slices. Added 5-HT, in the presence of the 5-HT uptake inhibitor chlorimipramine. caused a dose related inhibition of the K²⁺-evoked release of ³H]-5-HT in this system as did the 5-HT analogues 5-methoxytryptamine, N-methyltryptamine, 5-methoxy-NN'-dimethyltryptainine, N-methyl 5-hydroxytryptamine and tryptamine.The inhibitory effect of 1 μM 5-HT on the K⁺evoked release of ³H]-5-HT was reversed in a doserelated manner by the 5-HT antagonist drug, methiothepin (pA₁₀ value 6.7). At a concentration of 1 μM, the 5-HT antagonists drugs cinanserin and mianserin produced a small but significant reversal of the 5-HT induced inhibition of K⁺-evoked ³H]-5-HT release, but methysergide, metergoline and cyproheptadine were completely without effect at this concentration. The results are interpreted as evidence for a pre-junctional autoreceptor for 5-HT in the frontal cortex of the rat with a different pharmacological specificity for 5-HT antagonists from previously studied 5-HT receptors.