5-HT1C receptor antagonists have anxiolytic-like actions in the rat social interaction model

The effects of a range of 5-HT receptor antagonists were examined in an animal model of anxiety--the social interaction test. Six antagonists with high affinity for 5-HT1C receptors; mianserin, (+) mianserin, 1-naphthyl piperazine, ICI 169 369, pizotifen and LY 53857 all increased the time spent in active social interaction by pairs of weight-matched rats under high light unfamiliar conditions. As locomotion was only increased by 1-NP and then only at high doses, the effect of the drugs is consistent with anxiolysis. These properties were shared by the benzodiazepine anxiolytic chlordiazepoxide but not by the specific 5-HT2 antagonists ketanserin and altanserin, nor by the 5-HT1A and 5-HT1B antagonists cyanopindolol and pindolol. Similarly, neither the adrenergic alpha 2 antagonist idazoxan, the alpha 2 antagonist and putative 5-HT1D partial agonist yohimbine nor the H1 antagonist mepyramine had any significant effect. Since (+)mianserin, LY 53857 and ICI 169 369 at least have low affinity for 5-HT3 receptors these receptors are also unlikely to be involved. The results therefore imply that the observed anxiolytic effects of the drugs are likely to be mediated by 5-HT1C receptor blockade.