A method for assessing the effects of drugs on the central actions of 5-hydroxytryptamine.

Injection of 5-hydroxytryptophan into mice produces a characteristic head-twitch. For a given period of observation this response may be assessed quantitatively either by observing the proportion of mice showing at least one head-twitch (a quantal response) or by counting the number of head-twitches for each mouse (a graded response). A method, based on the quantal response, of investigating the effect of centrally acting compounds on the head-twitch response is described. Evidence is presented that the head-twitches are due to a central action of 5-hydroxytryptamine formed by decarboxylation of 5-hydroxytryptophan. Head-twitches are potentiated by monoamine oxidase inhibitors and by phenytoin. Antagonists tested include an inhibitor of decarboxylase, antagonists of 5-hydroxytryptamine, some antihistamines, major tranquillizers and analgesic and sympathomimetic drugs. Drugs which neither potentiate nor inhibit the response include barbiturates and minor tranquillizers. The method may be valuable in the preliminary examination of compounds likely to have a central action.