Abstract
The effects of three 5HT3 receptor antagonists: BRL 43964 (0.1 and 1 mg/kg, oral), GR 38032F (0.1 and 1 mg/kg, oral), and zacopride (0.01, 0.1 and 1 mg/kg, IP) were examined in low light test conditions of the social interaction test. None of the three 5HT3 receptor antagonists had a significant effect on social interaction. In contrast, in two experiments chlordiazepoxide (7.5 mg/kg) significantly increased social interaction and this effect was greatest in the unfamiliar test condition. In a third experiment, the effects of GR 38032F (0.1 and 1 mg/kg, oral) and zacopride (0.01, 0.1 and 1 mg/kg, oral) were investigated in the high light test conditions of the social interaction test; neither compound had a significant effect. In the elevated plus-maze, chlordiazepoxide (7.5 mg/kg oral or IP) significantly increased both the per cent number of entries made onto open arms and the per cent of time spent on the open arms, indicating an anxiolytic action. Zacopride (0.01, 0.1 and 1 mg/kg, oral or IP) had no significant effect in this test. The effect of the baseline rate of responding in the social interaction test on the effects of 5-HT3 antagonists is discussed. The results from the present experiment and those from other animal tests of anxiety caution against the conclusion that 5HT3 receptor antagonists are anxiolytic.
Similar content being viewed by others
References
Baldwin HA, File SE (1986) The elevated plus-maze test of anxiety: further behavioural validation. Psychopharmacology 89:S9
Brittain RT, Butler A, Coates IH, Fortune DH, Hagan R, Hill JM, Ireland SJ, Jack D, Jordan CC, Oxford A, Straughan DW, Tyers MB (1987) GR38032F, a novel selective 5HT3 receptor antagonist. Br J Pharmacol 90:87P
Costall B, Domeney AM, Gerrard PA, Kelly ME, Naylor RJ (1988) Zacopride: anxiolytic profile in rodent and primate models of anxiety. J Pharm Pharmacol 40:302–305
Donatsch P, Engel G, Richardson BP, Stadler P (1984) ICS 205-930: a highly selective and potent antagonist at peripheral neuronal 5-hydroxytryptamine (5-HT) receptors. Br J Pharmacol 81:34P
Fake CS, King FD, Sanger GJ (1987) BRL 43694: a potential novel 5-HT3 antagonist. Br J Pharmacol 91:335P
File SE (1987) The contribution of behavioural studies to the neuropharmacology of anxiety. Neuropharmacology 26:877–886
File SE (1988) How good is social interaction as a test of anxiety? In: Simon P, Soubrie P, Widlocher D (eds) Animal models of psychiatric disorders, vol 1. Karger, Basel, pp 151–166
File SE (1989) Preclinical studies of the mechanisms of anxiety and its treatment. In: Ballenger JC (ed) Neurobiological aspects of panic disorder. Liss, New York (in press)
File SE, Hyde JRG (1978) Can social interaction be used to measure anxiety? Br J Pharmacol 62:19–24
Guy AD, Gardner CR (1985) Pharmacological characterisation of a modified social interaction model of anxiety in the rat. Neuropsychobiology 13:194–200
Johnston AL, File SE (1988) Effects of ligands for specific 5HT receptor sub-types in two animals tests of anxiety. In: Lader M (ed) Buspirone: a new introduction to the treatment of anxiety. RSM Services Ltd, London, pp 31–41
Jones BJ, Costall B, Domeney AM, Kelly ME, Naylor RJ, Oakley NR, Tyers MB (1988) The potential anxiolytic activity of GR38032F, a 5-HT3 receptor antagonist. Br J Pharmacol 93:985–993
Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167
Piper D, Upton N, Thomas D, Nicholass J (1988) The effects of the 5-HT3 receptor antagonists BRL 43694 and GR 38032F in animal behavioural models of anxiety. Br J Pharmacol 94:314P
Smith WW, Sancilio LF, Owera-Atepo JB, Naylor RJ, Lambert L (1988) Zacopride, a potent 5HT3 antagonist. J Pharm Pharmacol 40:301–302
Spealman RD (1979) Comparison of drug effects on responding punished by pressurized air or electric shock delivery in squirrel monkeys: pentobarbital, chlordiazepoxide, d-amphetamine and cocaine. J Pharmacol Exp Ther 209:309–315
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
File, S.E., Johnston, A.L. Lack of effects of 5HT3 receptor antagonists in the social interaction and elevated plus-maze tests of anxiety in the rat. Psychopharmacology 99, 248–251 (1989). https://doi.org/10.1007/BF00442817
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00442817