| Up to present, a large number of reports
unveiled exacerbating effects of both long- and short-term
administration of morphine, as a potent analgesic agent, on
opium-addicted individuals and a plethora of cell kinetics,
although contradictory effect of morphine on different cells
have been introduced until yet. To address the potent
modulatory effect of morphine on neural multipotent precursors
with emphasis on endogenous sex-related neurosteroids
biosynthesis, we primed the rat neural stem cells
isolated from embryonic rat telencephalon to various concentrations
of morphine including 10, 20, 50 and 100 lM
alone or in combination with naloxone (100 lM) over
period of 72 h. Flow cytometric Ki-67 expression and
Annexin-V/PI based necrosis and apoptosis of exposed
cells were evaluated. The total content of dihydrotestosterone
and estradiol in cell supernatant was measured by
ELISA. According on obtained data, both concentrationand
time-dependent decrement of cell viability were
orchestrated thorough down-regulation of ki-67 and
simultaneous up-regulation of Annexin-V. On the other
hand, the addition of naloxone (100 lM), as Mu opiate
receptor antagonist, could blunt the morphine-induced
adverse effects. It also well established that time-course
exposure of rat neural stem cells with morphine potently
could accelerate the endogenous dihydrotestosterone and
estradiol biosynthesis. Interestingly, naloxone could consequently
attenuate the enhanced neurosteroidogenesis
time-dependently. It seems that our results discover a
biochemical linkage between an accelerated synthesis of
sex-related steroids and rat neural stem cells viability. |