Allosteric modulation of the effects of the 5-HT reuptake inhibitor escitalopram on the rat hippocampal synaptic plasticity.
The present in vivo electrophysiological studies in anesthetized rat were undertaken to assess the effects of the selective serotonin (5-HT) reuptake inhibitor (SSRI) escitalopram alone or in combination with the R-citalopram (the S- and R-enantiomers of citalopram), on both long-term potentiation (LTP) in the CA(1) region of dorsal hippocampus and spontaneous firing activity of dorsal raphe (DR) 5-HT neurons. At the postsynaptic level, neither escitalopram (10 mg/kg, i.p.) nor R-citalopram (20 mg/kg, i.p.) modified basal synaptic transmission but only escitalopram impaired LTP expression. Importantly, R-citalopram counteracted significantly the escitalopram-induced decrease of LTP. At the pre-synaptic level, escitalopram (25-75 microg/kg, i.v.) dose-dependently suppressed the spontaneous firing activity of DR 5-HT neurons and this suppressant effect was significantly prevented by a prior injection of R-citalopram (10 mg/kg, i.p.). These results support a role of allosteric binding sites of 5-HT transporter in the regulation of long-lasting CA(1) synaptic plasticity and DR 5-HT neuronal firing activity.
Mnie-Filali
Ouissame
O
Université Claude Bernard, Faculté de Pharmacie-Lyon 1, Laboratoire de Neuropharmacologie et Neurochimie, INSERM EA 512, 8, Rockefeller 69373, Lyon Cedex 08, France.
El Mansari
Mostafa
M
Espana
Agnès
A
Sànchez
Connie
C
Haddjeri
Nasser
N
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015283:Citalopram / Q000008:administration & dosage* / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000145:classification; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors