Effects of 5-HT4 receptor antagonists on rat behaviour in the elevated plus-maze test

The anxiolytic-like effects of a variety of 5-HT receptor agonists and antagonists have been intensively studied in animal models. However, no direct effects of agents modulating 5-HT4 receptors have been reported, in spite of their suggestive location in the brain. The objective of the present study was the determination of the effects of two selective 5-HT4 receptor antagonists, SB 204070 [1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate] and GR 113808 [[1-[2-methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl 1-methyl-1 H-indole-3-carboxylate], in the elevated plus-maze test in rats. Results have shown that both 5-HT4 receptor antagonists exhibit an anxiolytic-like profile, although only at the dose of 1.0 mg/kg (s.c.). At this dose, both compounds significantly increased the percentage of time spent in open arms exploration, while other variables evaluated remained unaffected at the dose range tested. Results suggest that 5-HT4 receptor antagonists could have some anxiolytic-like properties, although their effects seem more limited and less consistent than those presented by classic anxiolytics, such as diazepam. However, they are similar to those exhibited by granisetron [endo-1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1 H-indazole-3-carboxamide], a 5-HT3 receptor antagonist.