Stereoselective effects of (R)- and (S)-zacopride on cognitive performance in a spatial navigation task in rats.
Neuropharmacology
; 35(3): 321-7, 1996 Mar.
Article
em En
| MEDLINE
| ID: mdl-8783207
ABSTRACT
In the present studies we investigated the actions of (R)- and (S)-zacopride, potent 5-HT3 receptor antagonists with 5-HT4 receptor agonists properties, on performance in a spatial learning and memory task in rats, the Morris water maze. A significant cognitive/performance deficit, as indicated by the increased escape latency across several trials, was produced by systemic administration of the muscarinic receptor antagonist atropine (30 mg/kg, IP). (R)-zacopride (0.001-1 microgram/kg, but not 10 or 100 micrograms/kg) significantly reduced escape latency in atropine-treated animals. (S)-Zacopride was inactive over the entire dose range examined (0.001-100 micrograms/kg, i.p.). Moreover, pretreatment with (S)-zacopride (1 or 100 micrograms/kg) did not alter the procognitive effects of (R)-zacopride (1 microgram/kg). These data demonstrate that the cognition enhancing properties of zacopride in this model of cholinergic hypofunction are exclusive to its (R)-enantiomer and imply that this action is unrelated to 5-HT, receptor antagonism or 5-HT4 receptor agonism. The possibility that the procognitive effects of (R)-zacopride may be related to actions at the novel "(R)-zacopride site" is discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Atropina
/
Antagonistas da Serotonina
/
Benzamidas
/
Antagonistas Muscarínicos
/
Aprendizagem em Labirinto
/
Compostos Bicíclicos Heterocíclicos com Pontes
Limite:
Animals
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article