P1-436: Efficacy of the 5HT4 partial agonist SL65.0155 in the 5 choice serial reaction time task

5HT4 ligands are currently being developed for the symptomatic treatment of Alzheimer's disease (AD). This class of compound is known to improve learning and memory in a variety of assays including the object recognition and the Morris watermaze. These cognitive domains are known to be severely effected in AD and therefore compounds of this class my have utility in AD. However, other cognitive domains are also known to be severely effected in AD including attention / executive function. These studies defined the effects of a 5HT4 partial agonist (SL65.0155) in an assay of attention in rats, the 5 choice serial reaction time task. Rats were trained to criteria using standard protocols, training criteria used were <20% errors of omission, >80% correct using a stimulus duration of 1 second. Animals were treated with compounds using a crossover design protocol. Treatments were tested under baseline conditions in the 5CSRTT or using a protocol with reduced stimulus duration (1.0 – 0.1 seconds). SL65.0155 was tested at 0.1 and 1mg/kg (s.c.) given 120 minutes prior to the 5CSRTT assay, nicotine (0.2mg/kg s.c.) was included as a positive control in this study. Consistent with previously published data, nicotine produced statistically significant effects on several measures of attention in both the baseline and reduced stimulus duration protocols. These included reducing missed trials and responses latencies, together with an increase in correct and premature responses. SL65.0155 (0.1mg/kg) produced statistically significant effects on baseline protocols in measures of accuracy, reducing incorrect trials and increasing % correct trials; in addition perseverative responding was also reduced. Similar effects were also observed using the reduced stimulus duration protocol at the 0.5sec data point. These effects on accuracy of responding suggest that this class of compound, in addition to improving learning and memory, may also improve attention.