OBJECTIVE@#To reveal the effect and mechanism of Jiaotai Pill (, JTP) on insomniac
rats.@*
METHODS@#The insomniac model was established by
intraperitoneal injection of
p-chlorophenylalanine (PCPA). In behavioral experiments,
rats were divided into control, insomniac model, JTP [3.3 g/(kg•d)], and
diazepam [4 mg/(kg•d)] groups. The
treatment effect of JTP was evaluated by weight measurement (increasement of
body weight),
open field test (number of crossings) and forced
swimming test (immobility
time). A
high performance liquid chromatography-electrochemical
detection (
HPLC-ECD)
method was built to determine the concentration of monoamine transmitters in
hypothalamus and peripheral organs from normal, model, JTP,
citalopram [30 mg/(kg•d)],
maprotiline [40 mg/(kg•d)] and
bupropion [40 mg/(kg•d)] groups. Expressions of
serotonin transporter (SERT),
dopamine transporter (DAT), and
norepinephrine transporter (NET) were analyzed by quantitative
polymerase chain reaction (qPCR) and
Western blot in normal, model and JTP groups. A
high performance liquid chromatography-
electrospray ionization mass spectrometry (
HPLC-ESI-MS/MS)
method was established to determine the
pharmacokinetics,
urine cumulative excretion of
metformin in vivo, and
tissue slice uptake
in vitro, which were applied to assess the activity of organic
cation transporters (OCTs) in
hypothalamus and peripheral organs.@*RESULTS@#Compared with the insomniac model group, the
body weight and spontaneous locomotor were increased, and the immobility
time was decreased
after treatment with JTP (P<0.01). Both
serotonin and
dopamine contents in
hypothalamus and peripheral organs were increased (P<0.01). The
norepinephrine content was increased in peripheral organs and decreased in
hypothalamus (P<0.05 or P<0.01). At the same
time, SERT, DAT, OCT1, OCT2, and OCT3 were down-regulated in
hypothalamus and peripheral organs (P<0.05). NET was down-regulated in peripheral organs and up-regulated in
hypothalamus (P<0.05 or P<0.01). Moreover, the activity of OCTs in
hypothalamus and peripheral organs was inhibited (P<0.05).@*CONCLUSION@#JTP alleviates
insomnia through
regulation of monoaminergic system and OCTs in
hypothalamus and peripheral organs.