5-HT6 receptor antagonists enhance retention of a water maze task in the rat.
BACKGROUND
5-HT(6) receptors are predominantly located in the brain and may be involved in cognitive processes. The aim of this study was to assess the effects of two potent and selective 5-HT(6) receptor antagonists, SB-271046-A and SB-357134-A, on learning and memory in the rat.


METHODS
Spatial learning and memory was assessed by testing the effects of SB-271046-A and SB-357134-A on acquisition and retention of a water maze task.


RESULTS
In the water maze, administration of SB-271046-A or SB-357134-A (3 or 10 mg/kg) had no effect on learning per se. At 10 mg/kg, however, both compounds produced a significant improvement in retention of a previously learned platform position when tested 7 days after training. By contrast, the acetylcholinesterase inhibitor, Aricept (donepezil, 0.1, 0.3 mg/kg PO) had no effect in this task.


CONCLUSIONS
This study demonstrates that systemic administration of SB-271046-A and SB-357134-A produces improvements in retention of a water maze task in the rat. These data indicate that 5-HT(6) receptor antagonism may be involved in cognitive function.
Rogers
D C
DC
Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex CM19 5AW, UK. Derek_C_Rogers@sbphrd.com
Hagan
J J
JJ
D000818:Animals; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012153:Retention, Psychology / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013550:Swimming / Q000502:physiology; D013876:Thiophenes / Q000494:pharmacology; D000096926:Benzenesulfonamides
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C422502:N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide; D000096926:Benzenesulfonamides; C097216:serotonin 6 receptor; C117443:SB 271046