Effect of subchronic lithium treatment on citalopram-induced increases in extracellular concentrations of serotonin in the medial prefrontal cortex.
We investigated the effect of citalopram [a selective serotonin (5-HT) reuptake inhibitor; SSRI] and MKC-242 (a selective 5-HT1A agonist), following treatment with subchronic lithium (p.o., 1 week) on extracellular 5-HT concentrations in the medial prefrontal cortex (mPFC). Acute treatment with citalopram (3 and 30 mg/kg) led to significant increases in extracellular 5-HT concentrations. The subchronic lithium group showed significantly higher basal levels of extracellular 5-HT than normal diet controls. Acute citalopram (3 and 30 mg/kg) treatment together with subchronic lithium treatment showed significant increases in the extracellular 5-HT concentrations, compared with citalopram treatment alone. Acute MKC-242 (1 mg/kg) treatment showed significant decreases in extracellular 5-HT concentrations, in both the normal diet and lithium diet groups to the same extent. The addition of lithium did not change the effect of the 5-HT1A agonist on extracellular 5-HT concentrations. This study suggests that lithium augmentation of the antidepressant effect of SSRI is mediated by the additional increases in extracellular 5-HT concentrations following the co-administrations of lithium and SSRI.
Muraki
I
I
Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan. smuraki@mtj.biglobe.ne.jp
Inoue
T
T
Hashimoto
S
S
Izumi
T
T
Ito
K
K
Koyama
T
T
D000284:Administration, Oral; D000818:Animals; D015283:Citalopram / Q000008:administration & dosage*; D004146:Dioxanes / Q000008:administration & dosage; D004149:Dioxoles / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D008094:Lithium / Q000008:administration & dosage*; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage
D015283:Citalopram; D004146:Dioxanes; D004149:Dioxoles; D008094:Lithium; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C096294:osemozotan