Evaluation of the tocolytic effect of morphine in a mouse model of lipopolysaccharide-induced preterm delivery: The role of nitric oxide

Tocolytic Effect of Δ9-Tetrahydrocannabinol in Mice Model of Lipopolysaccharide—Induced Preterm Delivery: Role of Nitric Oxide

“…13,26,27 Our findings, in consistency with the previous observation of cannabinoids' relaxant function, demonstrated a clear preventive effect of THC on preterm delivery and showed the possible role of exogenous cannabinoids in the maintenance of uterine quiescence during LPS-induced preterm delivery. Similar to previous studies, 20,28 histopathological study showed severe inflammation accompanied by blood vessel dilatation in LPS-treated mice placenta, while in the placentas of THC-LPS treated mice, mild inflammation was observed without blood vessel dilatation. These observations also confirm the predominant role of THC in the decrease of preterm delivery rate in our study.…”

“…Neither maternal death nor severe depression of spontaneous movement was observed under the experimental conditions in the control group. According to the study by Javadi-Paydar et al, 20 pregnant mice revealed the highest (100%) incidence of preterm delivery when they were treated with 35 mg/kg LPS, twice at a 3hour interval on gd 15. In experiment (1), administration of THC (0.02, 0.05, 0.1, 0.5, and 1 mg/kg; twice), 1 hour before each LPS injection on gd 15, showed no effect on incidence of LPS-induced preterm delivery; injection of 5 mg/kg THC (twice on gd 15 before each LPS) caused death in all treated mice (data not shown).…”

“…Based on the method reported previously by Javadi-Paydar et al, 20 the pregnant mice were treated with 35 mg/kg of LPS, twice, at 2 and 5 PM (at 3-hour interval), on gd 15. Mice were observed in the early mornings and late afternoons the following days of the study.…”

“…To detect the involvement of NO pathway in the therapeutic potential role of THC in infection-mediated preterm birth, L-NAME (2 mg/kg) was administered 1 hour before THC (0.5 mg/kg; once at 1 PM) on gds 13 and 14 and 1 hour before the first dose of THC (0.5 mg/kg; twice at 1 and 4 PM) on gd 15. This dose of L-NAME was chosen based on a previous study by Javadi-Paydar et al 20 and a dose response of chronic L-NAME administration (2, 5, and 10 mg/kg, once, from gd 13 through gd 15; without THC and LPS) was accomplished in this study. To support our hypothesis that THC administration prior to LPS acts via the NO pathway, chronic THC 0.5 mg/kg (once, on gds 13 and 14, then twice on gd 15) was injected before effective dose of L-NAME (5 mg/kg, 1 hour after THC from gds 13 and 14 and the second dose of THC on gd 15).…”

Neurosteroid involvement in threatened preterm labour

“…When allopregnanolone acts centrally, it induces an inhibitory opioid mechanism that maintains the quiescence of the magnocellular oxytocin system. Morphine increases the duration of gestation and reduces the rate of preterm delivery in rats 23 . Moreover, blocking allopregnanolone production in late pregnancy leads to preterm labour in rats 24 …”