ACTIONS OF 5-HYDROXYTRYPTOPHAN TO INHIBIT AND DISINHIBIT MOUSE BEHAVIOR IN THE LIGHT DARK TEST/

The involvement of 5-HT receptors in behavioural responding to an aver sive situation was investigated in the mouse light/dark test. The admi nistration of 5-hydroxytryptophan (5-HTP) (12.5-50 mg/kg i.p.) increas ed brain 5-HT turnover and inhibited mouse behaviour in the light/dark test box. The 5-HT2C/5-HT2A receptor antagonists methysergide (1.0 an d 5.0 mg/kg i.p.) and ritanserin (0.1-1.0 mg/kg i.p.) antagonised (met hysergide) or reversed (ritanserin) the effects of 5-HTP to an increas ed exploration of the light compartment; a low dose of the 5-HT3 recep tor antagonist ondansetron (0.01 mg/kg i.p.) had a similar effect. The disinhibitory effect of the 5-HTP/ritanserin interaction was antagoni sed by the 5-HT3/5-HT4 receptor antagonists SDZ205-557 (0.001-0.1 mg/k g) and a high dose of tropisetron (1.0 mg/kg i.p.) but not by ondanset ron (1.0 mg/kg i.p.). At these doses tropisetron and ondansetron had n o effect in their own right. Thus the dominant effect of 5-HTP in the mouse is to inhibit behaviour, a response mediated via 5-HT2C/5-HT2A a nd 5-HT3 receptors. A 5-HT4 may effect an opposing disinhibitory poten tial as revealed by ritanserin.