Effects of acute and chronic administration of MCI-225, a new selective noradrenaline reuptake inhibitor with 5-HT3 receptor blocking action, on extracellular noradrenaline levels in the hypothalamus of stressed rats
Yl. Wu et al., Effects of acute and chronic administration of MCI-225, a new selective noradrenaline reuptake inhibitor with 5-HT3 receptor blocking action, on extracellular noradrenaline levels in the hypothalamus of stressed rats, JPN J PHARM, 83(1), 2000, pp. 31-38
In the present study, we investigated the effects of acute and chronic syst
emic administration of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperaziny
l)thieno[2,3-d]pyrimidine monohydrate hydrochloride), a newly-developed sel
ective noradrenaline (NA) reuptake inhibitor with 5-HT3-receptor-blocking a
ction, on extracellular NA levels in the hypothalamus of stressed and non-s
tressed rats by utilizing intracerebral microdialysis. Acute administration
of MCI-225 (3 and 10 mg/kg, p.o.) significantly and dose-dependently incre
ased extracellular NA levels in the hypothalamus in non-stressed rats. Foot
shock for 20 min also significantly increased NA levels in the hypothalamus
of both groups of rats pretreated with vehicle and MCI-225. Although chron
ic administration of MCI-225 (3 or 10 mg/kg, p.o. for 14 days) did not alte
r the basal extracellular NA levels in the hypothalamus, the stress-induced
increases in extracellular NA levels were significantly lower in rats chro
nically treated with MCI-225 (10 mg/kg) than those of rats pretreated with
vehicle for the same period. The increase in extracellular NA levels induce
d by MCI-225 challenge (3 or 10 mg/kg, p.o.) were not different between rat
s chronically treated with MCI-225 or vehicle. These results suggest that M
CI-225 enhances extracellular NA levels in the hypothalamus in both non-str
essed and stressed rats by inhibiting NA uptake and that chronic systemic a
dministration of MCI-225 did not alter basal extracellular NA levels, but r
educed the increase in NA release caused by footshock stress. These data su
ggest the possibility that MCI-225 might possess anxiolytic and/or antidepr
essant properties.