BIMU1 increases associative memory in rats by activating 5-HT4 receptors.
Olfactory association learning was used to investigate the involvement of 5-HT4 receptors in learning and long-term memory. The behavioral role of the 5-HT4 receptors was studied by using BIMU1 (3-ethyl-2,3-dihydro-N-[endo-8-methyl-8-azabicyclo(3.2.1)oct-3-yl]-2-oxo -1 H-benzimidazole-1-carboxamide, hydrochloride (Boehringer Ingelheim, Italy); a mixed 5-HT4 agonist/5-HT3 antagonist, and GR125487 (1-[2-[methyl sulphonyl)-amino]ethyl]-4-piperidinyl-methyl 5-fluro-2-methoxy-1H-indole-3- carboxylate; Glaxo Group Research, Hertfordshire, U.K.), a specific 5-HT4 antagonist. The intraperitoneal injections of BIMU1 at 1, 5, and 10 mg/kg were followed by an substantial improvement (> 15% in percentage of correct responses at the dose of 10 mg/kg) in associative memory. Difficulty rapidly reversing behavioral responses to previously learned association, 1 month later indicated that the BIMU1 effect at 10 mg/kg was not transient, but correlated to long-term memory. The effects of BIMU1 are most likely to be mediated by 5-HT4 receptors since they were blocked by GR125487 at 10 mg/kg. These data suggest that activation of 5-HT4 receptors may modulate cognitive processes like learning and memory.
Marchetti-Gauthier
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E
Laboratoire de Neurobiologie des Comportements-URA 372 CNRS, Université de Provence-IBHOP-Traverse Charles Susini, Marseille, France. nbc@newsup.univ-mrs.fr
Roman
F S
FS
Dumuis
A
A
Bockaert
J
J
Soumireu-Mourat
B
B
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012903:Smell / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology
D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C070187:(endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide; C082871:GR 113808