Lack of Effect of the 5-HT4 Receptor Ligands RS 67333 and RS 39604 on Murine Agonistic Behaviour

Robert Bell, Karl Lynch

School of Psychology, The Queen’s University of Belfast, Belfast, Northern Ireland.

DOI: 10.4236/jbbs.2012.21004                

Abstract

In comparison to studies investigating the roles of 5-HT1, 5-HT2 and 5-HT3 receptors in aggressive behaviour there is a dearth of material examining the function of 5-HT4 receptors in this behaviour. In view of this, the current study examined the effects of the 5-HT4 receptor partial agonist RS 67333 and antagonist RS 39604 in murine agonistic behaviour. RS 67333 failed to produce any significant changes in the offensive. Significant variation in the frequency of evade behaviour was detected but this occurred between treatment groups rather than with controls. Interestingly, both the frequency and duration of stretched attend behaviour were increased by RS 67333 0.1 mg/kg, a result indicative of increased risk assessment. The administration of RS 39604 (0.01 - 1 mg/kg) produced significant variation in the fre-quency and duration of following, and aggressive grooming. Frozen crouch behaviour was also increased significantly at 0.1 mg/kg. It is concluded that since the 5-HT4 receptor ligands employed in this study produced very few significant behavioural effects across the treatment groups, 5-HT4 receptors do not play a role in the modulation of murine aggressive behaviour.

Keywords

RS 67333; RS 39604; Agonistic Behaviour; Social Behaviour; Ethological Analysis

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	R. Bell and H. Hobson, “5-HT1A Receptor Influences On Rodent Social and Agonistic Behaviour: A Review and Empirical Study,” Neuroscience and Biobehavioural Reviews, Vol. 18, No. 3, 1994, pp. 325-333.
[2]	R. Bell, P. Mitchell and H. Hobson, “Effects of the 5-HT1A Antagonist (+)-WAY-100135 on Murine Social and Agonistic Behaviour,” Pharmacology, Biochemistry and Behavior, Vol. 54, No. 1, 1996, pp. 159-167. doi:10.1016/0091-3057(95)02168-X
[3]	R. Bell, P. Mitchell and K. Lynch, “Lack of Effect of the 5-HT1A Antagonist WAY-100635 on Murine Agonistic Behaviour,” Pharmacology, Biochemistry and Behavior, Vol. 64, No. 3, 1999, pp. 549-555. doi:10.1016/S0091-3057(99)00105-7
[4]	R. Bell, C. Donaldson and D. Gracey, “Differential Effects of CGS12066B and CP94-253 on Murine Social and Agonistic Behaviour,” Pharmacology, Biochemistry and Behavior, Vol. 52, No. 1, 1995, pp. 7-16. doi:10.1016/0091-3057(95)00077-A
[5]	D. Fontana, S. E. Daniels, E. Wong, R. D. Clark and R. Eglen, “The Effects of Novel Selective 5-Hydroxytryptamine (5-HT4) Receptor Ligands in Rat Spatial Navigation,” Neuropharmacology, Vol. 36, No. 4-5, 1997, pp. 689-696. doi:10.1016/S0028-3908(97)00055-5
[6]	G. Lucas, V. Rymar, J. Du, O. Mnie-Filali, C. Bisgaard, S. Manta, L. Lambas-Senas, O. Wiborg, N. Haddjeri, G. Pineyro, A. F. Sadikot and G. Debonnel, “Serotonin4 (5-HT4) Receptor Agonists Are Putative Antidepressants with a Rapid Onset of Action,” Neuron, Vol. 55, No. 5, 2007, pp. 712-725. doi:10.1016/j.neuron.2007.07.041
[7]	G. Lucas, J. Du, T. Romeas, O. Mnie-Filali, Haddjeri, G. Pineyro and G. Debonnel, “Selective Serotonin Reuptake Inhibitors Potentiate the Rapid Antidepressant-Like Effects of Serotonin 4 Receptor Agonists in the Rat,” PLoS One, Vol. 5, No. 2, 2010, p. e9253. doi:10.1371/journal.pone.0009253
[8]	J. S. Silvestre, A. G. Fernandez and J. M. Palacois, “Effects of 5-HT4 Receptor Antagonists on Rat Behaviour in the Elevated Plus-Maze Test,” European Journal of Pharmacology, Vol. 309, No. 3, 1996, pp. 219-222. doi:10.1371/journal.pone.0009253
[9]	H. M. Francis, N. J. Kraushaar, L. R. Hunt and J. L. Cornish, “Serotonin 5-HT4 Receptors in the Nucleus Accumbens Are Specifically Involved in the Appetite Suppressant and Not Locomotor Stimulant Effects of MDMA (‘Ecstasy’),” Psychopharmacology, Vol. 213, No. 2-3, 2011, pp. 355-363. doi:10.1007/s00213-010-1982-9
[10]	G. A. Kennett, F. Bright, B. Trail, T. P. Blackburn and G. Sanger, “Anxiolytic-Like Actions of the Selective 5-HT4 Receptor Antagonists SB204070 and SB207266A in Rats,” Neuropharmacology, Vol. 36, No. 4-5, 1997, pp. 707-712. doi:10.1016/S0028-3908(97)00037-3