Effects in the X-maze anxiety model of agents acting at 5-HT1 and 5-HT2 receptors

Three 5-HT agonists produced a dose-related fall in open/total arm entry ratio in the elevated X-maze model of anxiety at doses which did not affect total entries. The relative potency, 8-hydroxy-2-(di-n-propylamino)tetra lin (8-OH-DPAT) much greater than 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) greater than or equal to 5-methoxy-3(tetrahydropyridin-4-yl)1H-indole (RU 24969), was unrelated to the occurrence of wet dog shakes and suggests that 5-HT1 rather than 5-HT2 receptors may be involved. However, the 5-HT2 receptor antagonists ritanserin, ketanserin and seganserin caused an anxiolytic-like increase in entry ratio, although only ritanserin produced this effect across the dose range tested. +/- Pindolol, an antagonist at 5-HT1 receptors, showed a biphasic dose-response curve with a fall in entry ratio at one high dose. The effect of a submaximal dose of 8-OH-DPAT was prevented by pindolol but not by a similarly anxiolytic dose of ritanserin or diazepam. A higher dose of diazepam caused intense muscle hypotonia in combination with 8-OH-DPAT. Since open/total entry ratio appears to represent choice, rather than suppression or delay, of a response, the effects seen may indicate involvement of 5-HT receptors in anxiety separately from any change in the ability to withhold a response. The precise role of each receptor subtype, however, remains to be determined.