Anxiolytic-like effect after acute and subchronic administration of the selective 5-HT4 receptor partial agonist RS67,333

Resumen del póster presentado al 9th FENS: Forum of Neuroscience, celebrado en Milan (Italia) del 5 al 9 de julio de 2014.New pharmacological strategiesfor treating depression include 5-HT4 receptor agonists since theyare reported to have a faster onset of antidepressant actions versusconventional antidepressants. We have evaluated the anxiolytic profile of the5-HT4 receptor agonist RS67,333 (1.5, 3 and 6 mg/kg/day, i.p.) in C57/BL6mice after acute (30 min) and subchronic administration (3 days). Acute RS67,333induced a dose-dependent anxiolytic effect as evidenced by an increased centralactivity in the open field test: a) entries=23±4.5 (p<0.01); 31±4.3 (p<0.001) and 32±2.9 (p<0.001) for 1.5, 3 and 6 mg/kgof RS67,333 respectively vs 10±1.6for vehicle group, b) distance=3.0±0.4 (p<0.01); 4.3±0.6 (p<0.001) and 3.9±0.6 (p<0.001) for 1.5, 3 and 6 mg/kg of RS67,333 vs 1.1±0.2 for vehicle group, and c)time (s)= 25.8±4.6; 44.6±9.6 (p<0.05)and 57.0±9.0 (p<0.01) for 1.5, 3 and 6 mg/kg of RS67333 vs 20.8±3.0 for vehicle group. Interestingly, the anxiolyticprofile of RS67,333 is also observed 24 hours after 3-day subchronic administrationas evidenced by a significant reductionin the latency to feed in the novelty suppressed feeding (NSF), reaching themaximal effect with the dose of 6 mg/kg/day (% reduction= 59.9±3.1, p