RS 67333 and D-cycloserine accelerate learning acquisition in the rat.
Various 5-hydroxytryptamine (5-HT) central receptor subtypes have been implicated in cognitive performances. In the present investigation, we studied the effects of the selective 5-HT(4) receptor agonist RS 67333 (1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone; 1 mg/kg, i.p.) on spatial learning in the rat, and compared them to those of a reference drug, the partial NMDA receptor agonist D-cycloserine (10 mg/kg, i.p.). The effects of these two drugs were evaluated in four protocols which employed the Morris water maze task with various numbers of daily trials and inter-trial intervals (ITI; 4 trials with 30 s ITI; 2 trials with 2 h or 12 h ITI; or one daily trial). In the 2 trial-2 h ITI protocol, rats treated with RS 67333 or D-cycloserine exhibit a reduced mean swim distance during the first days of training when compared to controls. Neither RS 67333 nor D-cycloserine modified the acquisition performances in the 2 trial-12 h ITI or the one daily trial tests or the retention score measured in each protocol. These data suggest that RS 67333 and D-cycloserine can improve the learning rate in a high demand memory task and confirm that selective 5-HT(4) receptor ligands may provide novel approaches for the development of cognitive enhancers.
Lelong
V
V
Université de Caen, Laboratoire de Pharmacologie, Centre d'Etudes et de Recherche sur le Médicament de Normandie, UFR des Sciences Pharmaceutiques, 1 rue Vaubénard, 14032 Caen Cedex, France.
Dauphin
F
F
Boulouard
M
M
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D003523:Cycloserine / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000814:Aniline Compounds; D000963:Antimetabolites; D010880:Piperidines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; C107826:RS 67333; D003523:Cycloserine