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|Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat|
|Authors: ||Marcos, B. (Beatriz)|
Chuang, T.T. (Tsu T.)
Gil-Bea, F. (Francisco J.)
Ramirez, M. (María Javier)
|Keywords: ||Morris water maze|
|Issue Date: ||2008|
|Publisher: ||Wiley Blackwell|
|Publisher version: ||http://onlinelibrary.wiley.com/doi/10.1038/bjp.2008.281/abstract|
|Citation: ||Marcos B, Chuang TT, Gil-Bea FJ, Ramirez MJ. Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat. Br J Pharmacol 2008 Oct;155(3):434-440.|
|BACKGROUND AND PURPOSE:
The beneficial effect of 5-HT6 receptor antagonism in cognition remains controversial. This study has been undertaken to reassess the cognition enhancing properties of acute vs subchronic treatment with the selective 5-HT6 receptor antagonist SB-271046 in unimpaired rats, as well as against scopolamine (cholinergic-) or MK-801 (glutamatergic-mediated) deficits.
The Morris water maze was used, measuring behaviour acquisition and retention, and swim speed. Other behavioural measures included yawning and motor activity. SB-271046 was given acutely before each trial or subchronically for 7 days before the trials. The AChE inhibitor galanthamine was also used alone or in combination with SB-271046.
Subchronic treatment with SB-271046 improved acquisition in the Morris water maze, while the acute treatment only improved retention. Neither acute nor subchronic SB-271046 treatment reversed scopolamine-induced learning deficits. MK-801 induced learning impairment associated with a behavioural syndrome, reversed by acute, but not subchronic, SB-271046 treatment. Interestingly, combined treatment with galanthamine and SB-271046 reversed the scopolamine- or MK-801-induced learning impairments. Subchronic treatment with SB-271046 did not modify motor activity or the increased number of yawns, a cholinergic-mediated behaviour, induced by single administration of SB-271046.
CONCLUSIONS AND IMPLICATIONS:
These data suggest a potential therapeutic role of 5-HT6 receptor antagonists such as SB-271046, alone or in combination with galanthamine, in the treatment of cognitive dysfunction, such as those seen in Alzheimer's disease and schizophrenia.|
|Permanent link: ||http://hdl.handle.net/10171/20228|
|Appears in Collections:||DA - Farmacia - Farmacología - Artículos de revista|
DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista
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