title: 5-HT4 receptor agonism in the five-choice serial reaction time task.
abstract: 5-HT4 agonists are currently being developed for the treatment of Alzheimer's disease and have previously been demonstrated to improve cognitive performance in a variety of tests but none that specifically test attention. Here we characterise the 5-HT4 partial agonist SL65.0155 compared to the reference drug, nicotine, in a test that is used to measure attention in rats, the five-choice serial reaction time task (5CSRTT). SL65.0155 (0.1 or 1 mg/kg s.c) and nicotine (0.2 mg/kg s.c.) were tested in protocols using fixed or variable stimulus durations. SL65.0155 improved performance by virtue of reducing incorrect responses and increasing % correct trials. Perseverative responses were reduced by SL65.0155, and latency during incorrect trials was increased following treatment with 0.1 mg/kg SL65.0155. Nicotine, as previously reported, improved performance in several parameters in the 5CSRTT, including response latencies, errors of omission and correct responses in both the baseline and variable stimulus protocol. These data suggest 5-HT4 agonists may have beneficial effects on attention and thereby may be useful for the treatment of cognitive deficits.
authors.affiliation: Neurosciences CEDD, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM195AW, UK. Christopher.j.hille@gsk.com
authors.forename: Christopher
authors.initials: C
authors.lastname: Hille
authors.forename: Simon
authors.initials: S
authors.lastname: Bate
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.forename: Maria I
authors.initials: MI
authors.lastname: Gonzalez