Modulation of the extracellular 5-hydroxytryptamine brain concentrations by the serotonin and noradrenaline reuptake inhibitor, milnacipran - Microdialysis studies in rats
N. Bel et F. Artigas, Modulation of the extracellular 5-hydroxytryptamine brain concentrations by the serotonin and noradrenaline reuptake inhibitor, milnacipran - Microdialysis studies in rats, NEUROPSYCH, 21(6), 1999, pp. 745-754
We examined the effects of the administration of milnacipran, a dual inhibi
tor of serotonin (5-hydroxy-tryptamine, 5-HT) and noradrenaline uptake on t
he 5-HT output in rat brain. Local milnacipran administration increased the
5-HT output in frontal cortex and the midbrain raphe nuclei 7- and 10-fold
by a Ca2+- and tetrodotoxin-dependent mechanism. However, the subcutaneous
administration of milnacipran (1-60 mg/kg SC) elevated the 5-HT output muc
h less in these areas (200-230% of baseline at 60 mg/kg). In hypothalamus,
10 mg/kg SC raised 5-HT levels to 170%. The 5-HT1A antagonist WAY-100635 ca
used a small potentiation of the effects of milnacipran. The baseline 5-HT
output was unaffected by 2-week treatments with milnacipran (30 and 60 mg/k
g . day). The distinct regional profile and the lack of enhancement of its
effects by WAY-100635 and prolonged treatment suggest that milnacipran does
not exert its antidepressant action through an enhancement of the serotone
rgic function. [Neuropsychopharmacology 21:745-754,1999] (C) 1999 American
College of Neuropsychopharmacology. Published by Elsevier Science Inc.