5-HT4 receptor agonism in the five-choice serial reaction time task

Behav Brain Res. 2008 Dec 16;195(1):180-6. doi: 10.1016/j.bbr.2008.08.007. Epub 2008 Aug 13.

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.

MeSH terms

  • Animals
  • Attention / drug effects
  • Attention / physiology
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Choice Behavior / drug effects*
  • Choice Behavior / physiology
  • Dioxanes / administration & dosage
  • Dioxanes / pharmacology*
  • Injections, Subcutaneous
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Nicotine / administration & dosage
  • Nicotine / pharmacology
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology
  • Oxadiazoles / administration & dosage
  • Oxadiazoles / pharmacology*
  • Rats
  • Reaction Time / drug effects*
  • Reaction Time / physiology
  • Receptors, Serotonin, 5-HT4 / physiology
  • Serial Learning / drug effects*
  • Serial Learning / physiology
  • Serotonin 5-HT4 Receptor Agonists

Substances

  • 5-(8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-(1-(2-phenylethyl)-4-piperidinyl)-1,3,4-oxadiazol-2(3H)-one
  • Dioxanes
  • Nicotinic Agonists
  • Oxadiazoles
  • Serotonin 5-HT4 Receptor Agonists
  • Receptors, Serotonin, 5-HT4
  • Nicotine