The selective 5-HT_1A receptor agonist NLX-112 displays anxiolytic-like activity in mice

Anxiety is amongst the commonest neuropsychiatric disorders, and there is a large body of evidence to suggest that abnormalities in serotonergic function are involved in its pathogenesis. Several studies have implicated 5-HT_1A receptor activation in mitigating anxiety disorders, so this study investigated the acute effects of a highly selective, potent and efficacious 5-HT_1A receptor full agonist, NLX-112 (a.k.a. befiradol, F13640), in middle-aged C57bl/6 J male mice. Video tracking was used to measure several parameters including time spent in the open and closed arms of an elevated plus maze (EPM), distance travelled and thigmotaxis in an open field test (OFT). At 0.1 to 1.0 mg/kg s.c., NLX-112 markedly decreased thigmotaxis and increased exploratory behaviour in the OFT and EPM assays. Hence, at 0.3 mg/kg, NLX-112 augmented locomotor activity in the centre of an open field arena by 164% and increased the time spent in the open arms of the EPM by 119% of control. These results indicate that anxiety-like behaviours in mice are significantly diminished with low doses of NLX-112. NLX-112 may therefore possess anxiolytic properties which complement its known activity in models of movement disorders.