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Stereoselective effects of (R)- and (S)-zacopride on cognitive performance in a spatial navigation task in rats.
- Source :
-
Neuropharmacology [Neuropharmacology] 1996 Mar; Vol. 35 (3), pp. 321-7. - Publication Year :
- 1996
-
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.
- Subjects :
- Animals
Dose-Response Relationship, Drug
Drug Antagonism
Male
Rats
Rats, Sprague-Dawley
Stereoisomerism
Atropine pharmacology
Benzamides pharmacology
Bridged Bicyclo Compounds, Heterocyclic pharmacology
Maze Learning drug effects
Muscarinic Antagonists pharmacology
Serotonin Antagonists pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-3908
- Volume :
- 35
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 8783207
- Full Text :
- https://doi.org/10.1016/0028-3908(96)00191-8