Recent developments in 5HT-related pharmacology of animal models of anxiety

The proposed anxioselective drug, buspirone, interacts with 5HT1 receptors. An analogue, MJ 13805, produces a 5HT behavioural syndrome blocked by central 5HT pathway lesion. Both compounds inhibit 5HT neurone firing. An association of any such action with models of anxiety is not yet possible. Several compounds selective for 5HT receptor sub-types have been tested in models of anxiety. Ritanserin, a selective 5HT2 antagonist, shows activity in an emergence test but not conflict models. Preliminary clinical reports indicate qualitatively different anxiolytic activity from that of benzodiazepines. TVXQ 7821 is selective for 5HT1 receptors and has shown activity in several models of anxiety. 8OHDPAT and RU 24969 are 5HT1 agonists, selective for 5HT1A and 5HT1B sites respectively. 8OHDPAT released punished drinking but reversed a similar effect of PCPA. Its mode of action remains unclear. RU 24969 has shown no marked anxiolytic-like activity in food or water-motivated conflicts. Further studies are necessary before associating modulation of central 5HT systems with anxiolytic activity, either in animal models or patients.