213 93 93 4 4 M. A. E. Critchley S. L. Handley Drug Mechanisms Research Group, Pharmaceutical Sciences Institute Aston University B4 7ET Birmingham UK Abstract 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)≫5-methoxy-N,N-dimethyltryptamine (5-MeODMT)>=5-methoxy-3(tetrahydropyridin-4-yl)1H-indole (RU 24969), was unrelated to the occurrence of wet dog shakes and suggests that 5-HT 1 rather than 5-HT 2 receptors may be involved. However, the 5-HT 2 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-HT 1 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.
Psychopharmacology – Springer Journals
Published: Dec 1, 1987
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