Complete recovery of olfactory associative learning by activation of 5-HT4 receptors after dentate granule cell damage in rats.
Bilateral intradentate injections of 3.0microg of colchicine induced a substantial loss of granule cells and damage to the overlying pyramidal cell layer in region CA1 in adult male Long-Evans rats. All rats with such lesions showed a significant associative learning deficit in an olfactory discrimination task, while being unimpaired in the procedural component of this task. Injection of a partial selective 5-HT(4) agonist (SL65.0155; 0.01mg/kg, i.p., vs. saline) before the third of six training sessions enabled complete recovery of associative learning performance in the lesioned rats. Activation of 5-HT(4) receptors by a selective agonist such as SL65.0155 might therefore provide an opportunity to reduce learning and memory deficits associated with temporal lobe damage, and could be useful for the symptomatic treatment of memory dysfunctions related to pathological aging such as Alzheimer's disease.
Marchetti
E
E
Laboratoire de Neurobiologie des Processus Mnésiques, UMR 6149 CNRS Université de Provence, IFR 131 des Neurosciences et GDR 2905 du CNRS, Centre St. Charles, Pôle 3 C-3, Place Victor Hugo, 13331 Marseille Cedex 03, France.
Jacquet
M
M
Jeltsch
H
H
Migliorati
M
M
Nivet
E
E
Cassel
J C
JC
Roman
F S
FS
D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003078:Colchicine / Q000633:toxicity; D003714:Denervation; D018891:Dentate Gyrus / Q000473:pathology / Q000502:physiology; D004146:Dioxanes / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D010069:Oxadiazoles / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology*; D012193:Reversal Learning / Q000187:drug effects / Q000502:physiology; D058828:Serotonin 5-HT4 Receptor Agonists; D012903:Smell / Q000502:physiology*
C464499:5-(8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-(1-(2-phenylethyl)-4-piperidinyl)-1,3,4-oxadiazol-2(3H)-one; D004146:Dioxanes; D010069:Oxadiazoles; D058828:Serotonin 5-HT4 Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D003078:Colchicine