title: Effect of triiodothyronine (T(3)) augmentation of acute milnacipran administration on monoamine levels: an in vivo microdialysis study in rats.
abstract: BACKGROUND
  Up to 30% of depressed patients are partially or totally resistant to antidepressant therapy. The administration of triiodothyronine (T(3)) to antidepressant nonresponders can be an effective augmentation strategy, although the mechanism is not fully understood.
  
  
  METHODS
  In vivo microdialysis was used to examine the effect of T(3) augmentation of the antidepressant, milnacipran. Basal extracellular serotonin, norepinephrine, and dopamine levels were measured before and after acute milnacipran administration in the medial prefrontal cortex and amygdala of rats which had received subchronic (7 days) T(3) treatment or control saline.
  
  
  RESULTS
  Subchronic administration of T(3) at 0.1 mg/kg significantly increased basal extracellular levels of serotonin in the medial prefrontal cortex, but not in the amygdala. In contrast, subchronic administration of T(3) at 0.2 mg/kg did not alter basal extracellular serotonin levels in the medial prefrontal cortex. Basal extracellular levels of norepinephrine and dopamine were not modified by either dose of T(3) in either region. Acute administration of milnacipran, a serotonin-norepinephrine reuptake inhibitor, to control animals resulted in a significant increase of extracellular levels of serotonin, norepinephrine, and dopamine. When administered to animals treated subchronically with T(3) at 0.1 mg/kg, milnacipran produced an additional increase in extracellular serotonin levels but not in levels of norepinephrine or dopamine in the medial prefrontal cortex of rats.
  
  
  CONCLUSIONS
  These results suggest that the mechanism of the augmentation effect of milnacipran by T(3) administration occurs via enhancement of serotonergic neurotransmission, but not through noradrenergic or dopaminergic neurotransmission.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kitaichi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Shuken
authors.initials: S
authors.lastname: Boku
authors.forename: Akiko
authors.initials: A
authors.lastname: Kato
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
keywords: depression; in vivo microdialysis; milnacipran; monoamines; triiodothyronine