Hormonal probes of central serotonergic activity: do they really exist?

The response of a hormone allegedly under 5-hydroxytryptaminergic (5-HT-ergic) control to a compound stimulating or inhibiting serotonergic activity has been used as a measure of the functional state of central serotonergic systems. The relevant literature is reviewed, and based on that, it is concluded that, as yet, no reliable hormonal 5-HT probe exists. The main problems are nonselectivity of the challengers and noncomparability of individual studies because of variations in dose and route of administration. An acceptable hormonal 5-HT probe should at least have passed the following three tests. The influence of the challenger on catecholaminergic (CA) systems must be rendered unlikely in humans to avoid the pitfalls of, say, the 5-HT precursors whose CA-ergic influences have been overlooked. Dose-response relationships must be established to avoid the confusion caused by different investigators using the challenger in different doses. It must be demonstrated that the effect of the challenger is counteracted by its functional opponent.